Herbicidal aza bisphosphonic acids and compositions containing the same

ABSTRACT

Herbicidal compositions containing a bisphosphonic acid compound of the formula ##STR1## wherein n is 0, 1, 2, 3, 4, 5 or 6, or an agrochemically acceptable salt or hydrolyzable ester thereof and methods of controlling undesirable plant growth using these bisphosphonic acid containing compositions. The herbicidal compositions exhibit desirable efficacy when applied to plants post-emergence, but exhibit little significant activity when applied to plants pre-emergence. Novel aza-bisphosphonic acid compounds are also disclosed.

This application is a continuation-in-part of application Ser. No.08/133,722, filed Oct. 7, 1993, abandoned.

FIELD OF THE INVENTION

This invention relates to herbicidal compositions containing anaza-bisphosphonic acid wherein the nitrogen atom and the carbon atom towhich the two phosphonic acid groups are bound are linked by one toseven carbon atoms. In another aspect, this invention is directed to amethod of controlling the undesirable growth of plants by applying tothe area where control is desired an herbicidally effective amount ofsuch an aza-bisphosphonic acid composition. In yet another aspect, thisinvention is directed to certain novel aza-bis-phosphonic acidcompounds.

BACKGROUND OF THE INVENTION

The need for effective herbicides requires no special emphasis. Thecontrol of weeds and undesirable vegetation is of great economicimportance since weed competition inhibits the production of foliage,fruit or seed of agricultural crops. The presence of weeds can reduceharvesting efficiency and the quality of the harvested crop. Weeds onnoncropped areas may cause a fire hazard, undesirable drifting of sandor snow, and/or irritation to persons with allergies. Thus, suppressionof undesirable weed growth is very advantageous.

Moreover, it is highly desirable to possess herbicides which exhibitdesirable efficacy against plants when applied post emergently, butwhich further exhibit little significant activity when appliedpreemergently. Such herbicides will, for example, permit the control ofweeds already present in a field but will not harm crops which have notyet emerged.

Accordingly, it is an object of this invention to provide effectivenovel herbicidal compositions and a novel method of controlling weeds,as well as certain novel herbicidal compounds. It is a further object ofthis invention to provide novel compositions, methods and herbicidalcompounds which exhibit admirable postemergent control coupled with nosignificant preemergent control.

Japanese Patent Publication 54-147925 (Nissan Chemical) disclosesherbicidal bisphosphonic acid compounds wherein the phosphonic acidgroups are bound to a single carbon atom. Such compounds are of theformula: ##STR2## wherein X and Y are each hydrogen, halogen, alkyl orcycloalkyl; or salts thereof.

Herbicidal aza-bisphosphonic acid compounds wherein the carbon to whichthe two phosphonic acid groups are bound is directly linked to thenitrogen atom of the amino group are disclosed in U.S. Pat. No.4,447,256 (Suzuki et al.); British Patent 1,508,772 (Devlin); JapanesePatent Publication 54-37829 (Nissan Chemical); Japanese PatentPublication 54-144383 (Nissan Chemical); Japanese Patent Publication55-98105 (Nissan Chemical); and in "Herbicide Properties ofAminophosphonic Acid Derivatives", Dr. Y. Okamoto, 1st InternationalCongress on Phosphorus Compounds, Rabat, Oct. 17-21, 1977, pp. 649-652.

The phytocidal properties of aminophosphonates structurally related toN-(phosphonomethyl)glycine, including a compound having the molecularformula:

     (HO).sub.2 P(O)!.sub.2 C(NH.sub.2)CH.sub.2 N(C.sub.2 H.sub.5).sub.2,

are described in E. Bakuniak et al., "Further Studies on BiologicalActivity of Aminophosphonates Structurally Related toN-(Phosphonomethyl)glycine," Journal of Environmental Science andHealth, Vol. B18, Nos. 4 and 5, pp. 485-496 (1983).

Japanese Patent Publication 55-98193 discloses certain herbicidalcompounds of the formula ##STR3## wherein R is H, lower alkyl or halogenX is --CH₂ --, S or O; Y is H, lower alkyl or halogen; and alkali saltsthereof.

Although certain aza-bisphosphonic acid compounds wherein the carbon towhich the two phosphonic acid groups are bound is linked to a nitrogenatom via one or more carbon atoms have been disclosed in the art, theseparticular compounds are not indicated to have herbicidal activity.Thus, U.S. Pat. No. 3,962,318 discloses compounds useful as flameretardants, and German Patent DE 2754821 discloses compounds useful aschelators in water treatment. U.S. Pat. No. 5,133,972, U.S. Pat. No.4,990,503, U.S. Pat. No. 4,254,114, U.S. Pat. No. 4,666,895, U.S. Pat.No. 4,927,814, U.S. Pat. No. 4,939,130, U.S. Pat. No. 4,942,157,European Patent Publication 96,931, European Patent Publication 96,933,European Patent Publication 186,405, European Patent Publication 274,158, European Patent Publication 522,576, European Patent Publication513,760, PCT Patent Publication WO 93/24500, German Patent PublicationDE 3,804,686 and German Patent Publication DE 3,626,058 all disclosepharmaceutical uses for the specific compounds disclosed therein.

SUMMARY OF THE INVENTION

In one aspect, this invention is directed to an herbicidal compositioncomprising:

(A) an herbicidally effective amount of a compound of the Formula (I):##STR4## wherein n is 0, 1, 2, 3, 4, 5 or 6; R¹ is hydrogen, hydroxy, C₁-C₄ alkoxy, halogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl, hydroxy-C₁ -C₄-alkyl, hydroxy-C₁ -C₄ -alkoxy or N(R⁸)(R⁹) wherein R⁸ and R⁹ are eachindependently hydrogen or C₁ -C₃ alkyl;

each R², R³, R⁴ and R⁵ is independently hydrogen; hydrocarbyl;substituted hydrocarbyl; hydrocarbyloxy substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; or substituted hydrocarbyl-S(O)_(m) --;

R⁶ and R⁷ are each independently hydrogen; hydrocarbyl; substitutedhydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; substituted hydrocarbyl-S(O)_(m) --; pyridyl;substituted pyridyl; or are of the formula N(R¹²)(R¹³) wherein R¹² andR¹³ are independently hydrogen, hydrocarbyl or substituted hydrocarbyl;or

R⁶ and R⁷ together with the nitrogen to which they are bound form anaziridine; piperazine; morpholine; thiomorpholine; thiomorpholinesulfinyl; thiomorpholine sulfonyl; hexamethyleneimine; piperidine,tetrahydropyridine; pyrazole; imidazole; pyrrole; triazole;tetrahydropyrimidine; dihydroimidazole; pyrroline; azetidine;perhydroindole; perhydroquinoline; perhydroisoquinoline or pyrrolidinering; any of which may be optionally substituted with C₁ -C₁₂ alkyl,halo, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, C₆ -C₁₀ aryl, C₆-C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇-C₆ arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or

R⁴ and R⁶ or R² and R⁶ together with the nitrogen and carbon atoms towhich they are bound form an aziridine; piperazine; morpholine,thiomorpholine; thiomorpholine sulfinyl; thiomorpholine sulfonyl;hexamethyleneimine; piperidine, tetrahydropyridine; pyrazole; imidazole;pyrrole; triazole, tetrahydropyrimidine; dihydroimidazole; pyrroline;azetidine; perhydroindole; perhydroquinoline; perhydroisoquinoline; orpyrrolidine ring; any of which may be optionally substituted with C₁-C₁₂ alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆-C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo or C₁ -C₆, alkyl,nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀alkylsulfonyl, phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl,C₂ -C₁₀ alkenyl or cyano; or

R² and R⁴ together with the carbon atoms to which they are bound form aC₅ -C₆ cycloalkyl or cycloalkenyl ring; any of which may be optionallysubstituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁-C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo orC₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀ alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀alkylthio, C₁ -C₁₀ alkylsulfonyl, phenoxy, phenoxy substituted with haloor C₁ -C₆ alkyl, C₂ -C₁₀ alkenyl or cyano; or

R⁴ and R⁵ together form a 3-6 membered carbocyclic ring, optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆alkylthio or N(R¹⁰)(R¹¹) wherein R¹⁰ and R¹¹ are each independentlyhydrogen or C₁ -C₁₂ alkyl; and

m is 0, 1 or 2;

or an agrochemically acceptable salt or hydrolyzable ester thereof;

with the proviso that when n is 0, R⁴ and R⁵ are both hydrogen and R⁶and R⁷ are both --C₂ H₅, R¹ is not --NH₂ ; and

(B) an agrochemically acceptable carrier therefor.

In another aspect this invention is directed to a method of controllingthe growth of plants comprising applying to the locus of such plants anherbicidally effective amount of a compound of the Formula (I): ##STR5##wherein n is 0, 1, 2, 3, 4, 5 or 6; R¹ is hydrogen, hydroxy, C₁ -C₄alkoxy, halogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl, hydroxy-C₁ -C₄ -alkyl,hydroxy-C₁ -C₄ -alkoxy or N(R⁸)(R⁹) wherein R⁸ and R⁹ are eachindependently hydrogen or C₁ -C₃ alkyl;

each R², R³, R⁴ and R⁵ is independently hydrogen; hydrocarbyl;substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; or substituted hydrocarbyl-S(O)_(m) --;

R⁶ and R⁷ are each independently hydrogen; hydrocarbyl; substitutedhydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; substituted hydrocarbyl-S(O)_(m) --; pyridyl;substituted pyridyl; or are of the formula N(R¹²)(R¹³) wherein R¹² andR¹³ are independently hydrogen, hydrocarbyl or substituted hydrocarbyl;or

R⁶ and R⁷ together with the nitrogen to which they are bound form anaziridine; piperazine; morpholine; thiomorpholine; thiomorpholinesulfinyl; thiomorpholine sulfonyl; hexamethyleneimine; piperidine,tetrahydropyridine; pyrazole; imidazole; pyrrole; triazole;tetrahydropyrimidine; dihydroimidazole; pyrroline; azetidine;perhydroindole; perhydroquinoline; perhydroisoquinoline or pyrrolidinering; any of which may be optionally substituted with C₁ -C₁₂ alkyl,halo, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, C₆ -C₁₀ aryl, C₆-C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇-C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁-C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or

R⁴ and R⁶ or R² and R⁶ together with the nitrogen and carbon atoms towhich they are bound form an aziridine; piperazine; morpholine,thiomorpholine; thiomorpholine sulfinyl; thiomorpholine sulfonyl;hexamethyleneimine; piperidine, tetrahydropyridine; pyrazole; imidazole;pyrrole; triazole, tetrahydropyrimidine; dihydroimidazole; pyrroline;azetidine; perhydroindole; perhydroquinoline; perhydroisoquinoline; orpyrrolidine ring; any of which may be optionally substituted with C₁ -C₂alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆ -C₁₀aryl, C₆ -C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl,nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀alkylsulfonyl, phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl,C₂ -C₁₀ alkenyl or cyano; or

R² and R⁴ together with the carbon atoms to which they are bound form aC₅ -C₆ cycloalkyl or cycloalkenyl ring; any of which may be optionallysubstituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁-C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo orC₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀alkylthio, C₁ -C₁₀ alkylsulfonyl, phenoxy, phenoxy substituted with haloor C₁ -C₆ alkyl, C₂ -C₁₀ alkenyl or cyano; or

R⁴ and R⁵ together form a 3-6 membered carbocyclic ring, optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆alkylthio or N(R¹⁰)(R¹¹) wherein R¹⁰ and R¹¹ are each independentlyhydrogen or C₁ -C₁₂ alkyl; and

m is 0, 1 or 2;

or an agrochemically acceptable salt or hydrolyzable ester thereof;

with the proviso that when n is 0, R⁴ and R⁵ are both hydrogen and R⁶and R⁷ are both --C₂ H₅, R¹ is not --NH₂.

In yet another aspect, this invention is directed to novelaza-bisphosphonic acid compounds having a structure within the scope ofFormula (I) above.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The compounds employed in the herbicidal compositions of this inventionare of the Formula (I): ##STR6## wherein n is 0, 1, 2, 3, 4, 5 or 6; R¹is hydrogen, hydroxy, C₁ -C₄ alkoxy, halogen, C₁ -C₄ alkyl, C₁ -C₄haloalkyl, hydroxy-C₁ -C₄ -alkyl, hydroxy-C₁ -C₄ -alkoxy or N(R⁸)(R⁹)wherein R⁸ and R⁹ are each independently hydrogen or C₁ -C₃ alkyl;

each R², R³, R⁴ and R⁵ is independently hydrogen; hydrocarbyl;substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; or substituted hydrocarbyl-S(O)_(m) --;

R⁶ and R⁷ are each independently hydrogen; hydrocarbyl; substitutedhydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; substituted hydrocarbyl-S(O)_(m) --; pyridyl;substituted pyridyl; or are of the formula N(R¹²)(R¹³) wherein R¹² andR¹³ are independently hydrogen, hydrocarbyl or substituted hydrocarbyl;or

R⁶ and R⁷ together with the nitrogen to which they are bound form anaziridine; piperazine; morpholine; thiomorpholine; thiomorpholinesulfinyl; thiomorpholine sulfonyl; hexamethyleneimine; piperidine,tetrahydropyridine; pyrazole; imidazole; pyrrole; triazole;tetrahydropyrimidine; dihydroimidazole; pyrroline; azetidine;perhydroindole; perhydroquinoline; perhydroisoquinoline or pyrrolidinering; any of which may be optionally substituted with C₁ -C₁₂ alkyl,halo, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, C₆ -C₁₀ aryl, C₆-C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇-C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁-C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or

R⁴ and R⁶ or R² and R⁶ together with the nitrogen and carbon atoms towhich they are bound form an aziridine; piperazine; morpholine,thiomorpholine; thiomorpholine sulfinyl; thiomorpholine sulfonyl;hexamethyleneimine; piperidine, tetrahydropyridine; pyrazole; imidazole;pyrrole; triazole, tetrahydropyrimidine; dihydroimidazole; pyrroline;azetidine; perhydroindole; perhydroquinoline; perhydroisoquinoline; orpyrrolidine ring; any of which may be optionally substituted with C₁-C₁₂ alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆-C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl,nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀alkylsulfonyl, phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl,C₂ -C₁₀ alkenyl or cyano; or

R² and R⁴ together with the carbon atoms to which they are bound form aC₅ -C₆ cycloalkyl or cycloalkenyl ring; any of which may be optionallysubstituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁-C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo orC₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀alkylthio, C₁ -C₁₀ alkylsulfonyl, phenoxy, phenoxy substituted with haloor C₁ -C₆ alkyl, C₂ -C₁₀ alkenyl or cyano; or

R⁴ and R⁵ together form a 3-6 membered carbocyclic ring, optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, C₁ -C₆alkylthio or N(R¹⁰)(R¹¹) wherein R¹⁰ and R¹¹ are each independentlyhydrogen or C₁ -C₁₂ alkyl; and

m is 0, 1 or 2;

or an agrochemically acceptable salt or hydrolyzable ester thereof;

with the proviso that when n is 0, R⁴ and R⁵ are both hydrogen and R⁶and R⁷ are both --C₂ H₅, R¹ is not --NH₂.

Preferably:

R¹ is hydrogen, hydroxy, halogen or C₁ -C₄ alkyl;

R², R³, R⁴ and R⁵ are independently hydrogen; C₁ -C₂ alkyl; C₂ -C₁₂alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl, halo-C₂ -C₁₂ alkenyl;halo-C₂ -C₁₂ -alkynyl; C₆ -C₁₄ aralkyl; C₁ -C₁₂ alkoxy; or C₁ -C₁₂alkylthio;

R⁶ and R⁷ are independently hydrogen; C₁ -C₁₂ alkyl; C₂ -C₁₂ alkenyl; C₂-C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl; halo-C₂ -C₁₂ alkenyl; halo-C₂ -C₁₂alkynyl; pyridyl; substituted pyridyl; phenyl; substituted phenyl; C₆-C₁₄ aralkyl; substituted C₆ -C₁₄ aralkyl; C₁ -C₁₂ alkoxy or C₁ -C₁₂alkylthio; or

R² and R⁴ together with the carbon atoms to which they are bound form anoptionally substituted C₅ -C₆ cycloalkyl or cycloalkenyl ring; or

R⁴ and R⁶ together with the nitrogen and carbon atoms to which they arebound form a 3- to 7-membered ring optionally substituted with halogen,hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkylthio or C₇ -C₁₆ aralkyl; or

R⁶ and R⁷ together with the nitrogen to which they are bound form a 3-to 7-membered ring, optionally substituted with halogen, hydroxy, C₁ -C₆alkoxy, nitro, C₁ -C₆ alkyl, C₇ -C₁₆ aralkyl or C₁ -C₆ alkylthio groups;and

n is 0, 1, 2 or 3.

More preferably,

R¹ is hydrogen or hydroxy;

R² and R³ are hydrogen;

R⁴ and R⁵ are each independently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenylor C₆ -C₁₀ aralkyl optionally substituted with halogen or hydroxy; and

R⁶ and R⁷ are each independently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl,or C₆ -C₁₀ aralkyl optionally substituted with halogen or hydroxy; or

R⁴ and R⁶ together with the nitrogen and carbon atoms to which they arebound form a pyrrolidine or piperidine ring, either of which may beoptionally substituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆alkyl; or

R⁶ and R⁷ together with the nitrogen to which they are bound form apyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl; and

n is 0 or 1.

Particularly preferred compounds for use in the herbicidal compositionsand method of this invention include:

2-(R-alpha-methylbenzylamino)ethane-1,1-bisphosphonic acid;

2-(2-methylpropylamino)ethane-1,1-bisphosphonic acid;

2- 1-(4-methyl-1,3-imidazolyl)!ethane-1,1-bisphosphonic acid;

2-(1-pyrrolidinyl)ethane-1,1-bisphosphonic acid;

2-(piperidinyl)ethane-1,1-bisphosphonic acid;

2-(propylamino)ethane-1,1-bisphosphonic acid;

2-(N-methyl-N-ethylamino)ethane-1,1-bisphosphonic acid;

2-(n-butylamino)ethane-1,1-bisphosphonic acid;

2-(2-propenylamino)ethane-1,1-bisphosphonic acid;

2- 1-(1,2,3,6-tetrahydropyridinyl)!ethane-1,1-bisphosphonic acid; and

2-(N,N-dipropylamino)ethane-1,1-bisphosphonic acid;

3-(benzylamino)propane-1,1-bisphosphonic acid;

3-(1-pyrrolidino)propane-1,1-bisphosphonic acid;

3-(N-methyl-N-propylamino)propane-1,1-bisphosphonic acid;

3-(N-methyl-N-isobutylamino)propane-1,1-bisphosphonic acid;

3-(alpha-methylbenzylamino)propane-1,1-bisphosphonic acid;

3-(1-cyclohexylethylamino)propane-1,1-bisphosphonic acid;

(4-methyl-3-amino)pentane-1,1-bisphosphonic acid;

(4-methyl-3-benzylamino)pentane-1,1-bisphosphonic acid;

3-aminooctane-1,1-bisphosphonic acid;

4-(benzylamino)hexane-1,1-bisphosphonic acid;

2-(2-pyrrolidino)ethane-1,1-bisphosphonic acid;

2-(2-piperidino)ethane-1,1-bisphosphonic acid;

2- 2-(4-methyl)piperidino!ethane-1,1-bisphosphonic acid; and

2-(2-pyrrolidino)-1-hydroxyethane-1,1-bisphosphonic acid.

In another aspect, this invention is directed to certain classes ofnovel azabisphosphonic acid compounds within the scope of Formula 1.

One of such classes of novel aza-bisphosphonic acid compounds within thescope of this invention include those of the structural Formula II:##STR7## wherein R¹⁴ and R¹⁵ are each independently hydrogen, C₁ -C₆straight chain or branched alkyl, hydroxy, C₃ -C₆ alkenyl, C₁ -C₆ alkoxyor C₁ -C₆ alkoxy-C₁ -C₆ alkyl; and agriculturally acceptable saltsthereof. Specific compounds within the scope of this genus include:

2-(N,N-di-n-butylamino)ethane-1,1-bisphosphonic acid;

2-(N,N-diethylamino)ethane-1,1-bisphosphonic acid;

2-(N,N-di-n-propylamino)ethane-1,1-bisphosphonic acid;

2-(propylamino)ethane-1,1-bisphosphonic acid;

2-(isopropylamino)ethane-1,1-bisphosphonic acid;

2-(propylamino)ethane-1,1-bisphosphonic acid, tetrabutylammonium salt;

2-(propylamino)ethane-1,1-bisphosphonic acid, tributylamine salt;

2-(t-butylamino)ethane-1,1-bisphosphonic acid;

2-(n-butylamino)ethane-1,1-bisphosphonic acid;

2-(n-hexylamino)ethane-1,1-bisphosphonic acid, tetrabutylammonium salt;

2-(but-3-enylamino)ethane-1,1-bisphosphonic acid;

2-(n-hexylamino)ethane-1,1-bisphosphonic acid;

2-(isobutylamino)ethane-1,1-bisphosphonic acid;

2-(n-ethylamino)ethane-1,1-bisphosphonic acid;

2-(prop-2-enylamino)ethane-1,1-bisphosphonic acid;

2-(methoxyamino)ethane-l. 1-bisphosphonic acid;

2-(N-methoxy-N-methylamino)ethane-1,1-bisphosphonic acid;

2-(N-hydroxy-N-methylamino)ethane-1,1-bisphosphonic acid; and

2-(2-ethoxyethylamino)ethane-1,1-bisphosphonic acid;

Novel aza-bisphosphonic acids within the scope of this invention alsoinclude those of Formula III: ##STR8## wherein q is 0-10; j is 0-3; R¹⁶and R¹⁷ are each independently hydrogen or C₁ -C₆ alkyl; Ar is benzene,pyridine, pyrimidine, pyridazine, naphthalene, pyrazole, imidazole,triazole, thiazole, furan, thiophene, pyrrole, oxazole or thiadiazole;R¹⁸ is halo, C₁ -C₁₀ alkyl, aryl, substituted aryl, benzyl, substitutedbenzyl, nitro, halo-C₁ -C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio,C₁ -C₁₀ alkylsulfenyl, phenoxy, substituted phenoxy, C₂ -C₁₀ alkenyl orcyano; and R¹⁹, R¹⁰ and R²¹ are each independently hydrogen, C₁ -C₁₀alkyl, C₁ -C₁₀ substituted alkyl, C₇ -C₁₀ aralkyl or C₂ -C₁₀ alkenyl;and agriculturally acceptable salts thereof.

When q is 2 or more, each R¹⁶ and R¹⁷ may themselves independently behydrogen or C₁ -C₃ alkyl. Similarly, when j is 2 or more, each R¹⁸ maybe the same or different.

Specific compounds within the scope of this genus include:

2-(alpha-methylbenzylamino)ethane-1,1-bisphosphonic acid:

2-(2-methylbenzylamino)ethane-1,1-bisphosphonic acid;

2-(3-methylbenzylamino)ethane-1,1-bisphosphonic acid;

2-(2-phenylethylamino)ethane-1,1-bisphosphonic acid;

2-(benzylamino)ethane-1,1-bisphosphonic acid;

2-(S-alpha-methylbenzylamino)ethane-1,1-bisphosphonic acid; and

2-(R-alpha-methylbenzylamino)ethane-1,1-bisphosphonic acid, tetrabutylammonium salt.

Yet another novel genus of compounds within the scope of this inventionare compounds of Formula (IV): ##STR9## wherein A is an alkylenideneradical of 3-6 carbon atoms optionally substituted with C₁ -C₆ alkyl,and agriculturally acceptable salts thereof. Specific compounds withinthe scope of this genus include:

2-(1-pyrrolidinyl)ethane-1,1-bisphosphonic acid;

2-(2,5-dimethyl-1-pyrrolidinyl)ethane-1,1-bisphosphonic acid;

2-(1-pyrrolidinyl)ethane-1,1-bisphosphonic acid, tetramethylammoniumsalt;

2-(1-pyrrolidinyl)ethane-1,1-bisphosphonic acid tributylamino salt;

2-(1-pyrrolidinyl)ethane-1,1-bisphosphonic acid trimethylsulfonium salt;

2-(1-hexamethyleneiminyl)ethane-1,1-bisphosphonic acid;

2-(4-methyl-1-piperidinyl)ethane-1,1-bisphosphonic acid;

2-(2-methyl-1-piperidinyl)ethane-1,1-bisphosphonic acid; and

2-(3-methyl-1-piperidinyl)ethane-1,1-bisphosphonic acid.

Another novel genus of compounds within the scope of this invention arethose of Formula (V): ##STR10## wherein R²² is hydrogen or hydroxyl; andB is a C₂ -C₄ alkylidene linking group, optionally substituted with C₁-C₆ alkyl; and agriculturally acceptable salts thereof.

Specific compounds within the scope of this genus include:

1-(2-piperidinyl)-1-hydroxymethane-1,1-bisphosphonic acid;

1-(2-pyrrolidinyl)-1-hydroxymethane-1,1-bisphosphonic acid; and

1-(2-pyrrolidinyl)-1-hydroxymethane-1,1-bisphosphonic acid.

Another class of compounds within the scope of this invention are thoseof Formula VI: ##STR11## wherein R²³ and R²⁴ are each independentlyC1-C6 alkyl or together constitute a C₃ -C5 alkylidene group optionallysubstituted with C₁ -C₆ alkyl; and agrochemically acceptable saltsthereof.

Illustrative compounds within the scope of this invention include:

2-amino-1-hydroxy-2-methylpropane-1,1-bisphosphonic acid, hydrochloridesalt; and

1-(1-aminocyclopentyl)-1-hydroxymethane-1,1-bisphosphonic acid.

Yet another novel genus of compounds within the scope of this inventionare compounds of Formula (VII): ##STR12## wherein t is 2, 3 or 4; R²⁵and R²⁶ are each independently hydrogen, C₁ -C₁₀ alkyl, halo, nitro, C₁-C₉ alkoxy, C₁ -C₁₀ aralkyl, cyano, trifluoromethyl or represent a unitof unsaturation; and R²⁷ is hydrogen, C₁ -C₆ alkyl, C₇ -C₁₀ aralkyl,halo, nitro, trifluoromethyl or cyano. Each R²⁵ and R²⁶ may themselvesbe different members of the group listed above.

Illustrative compounds within the scope of this invention include:

2- 1-(2-methyl-1,4,5,6tetrahydro-1,3-pyrimidinyl)!ethane-1,1,bisphosphonic acid; and

2- 1-(4-methyl-1,3-imidazolyl)!ethane-1,1-bisphosphonic acid.

In still another aspect, this invention is directed to novelaza-bisphosphonic acid compounds of the Formula (VIII): ##STR13##wherein n is 1, 2, 3, 4, 5 or 6;

each R², R³, R⁴ and R⁵ is independently hydrogen; hydrocarbyl;substituted hydrocarbyl; hydrocarbyloxy,; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; or substituted hydrocarbyl-S(O)_(m) --;

R⁶ and R⁷ are each independently hydrogen; hydrocarbyl; substitutedhydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; substituted hydrocarbyl-S(O)_(m) --; pyridyl;substituted pyridyl; or are of the formula N(R¹⁰)(R¹¹) wherein R¹⁰ andR¹¹ are independently hydrogen, hydrocarbyl or substituted hydrocarbyl;or

R² and R⁴ or R⁴ and R⁶ or R⁶ and R⁷ or R⁴ and R⁵ form an optionallysubstituted 3- to 7-membered ring as defined above;

m is 0, 1 or 2; and

agrochemically acceptable salts thereof;

with the proviso that when n is 1, at least one of R², R³, R⁴, R⁵, R⁶and R⁷ is not H.

Preferred novel compounds of Formula VIII are those in which

n is 1, 2 or 3;

R², R³, R⁴ and R⁵ are each independently hydrogen; C₁ -C₁₂ alkyl; C₂-C₁₂ alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ -alkyl; halo-C₂ -C₁₂-alkenyl; halo-C₂ -C₁₂ -alkynyl; C₆ -C14 aralkyl; C₁ -C₁₂ alkoxy; or C₁-C₁₂ alkylthio;

R⁶ and R⁷ are each independently hydrogen; C₁ -C₁₂ alkyl; C₂ -C₁₂alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ -alkyl; halo-C₂ -C₁₂ -alkenyl;halo-C₂ -C₁₂ -alknyl; C₆ -C₁₄ aralkyl; C₁ -C₁₂ alkoxy; or C₁ -C₁₂alkylthio; or

R² and R⁴ together with the carbon atoms to which they are bound form anoptionally substituted C₅ -C₆ cycloalkyl or cycloalkenyl ring; or

R⁶ and R⁷ together with the nitrogen to which they are bound form a 3-to 7-membered ring, optionally substituted with halogen, hydroxy, C₁ -C₆alkyl; C₁ -C₆ alkylthio or C₆ -C₁₀ aralkyl;

and agrochemically acceptable salts and hydrolyzable esters thereof.

More preferred novel compounds of Formula (VIII) are those wherein:

n is 1;

R² and R³ are each hydrogen;

R⁴ and R⁵ are each independently hydrogen; C₁ -C₈ alkyl; C₂ -C₈ alkenyl;or C₆ -C₁₀ aralkyl optionally substituted with halogen or hydroxy;

R⁶ and R⁷ are each independently hydrogen; C₁ -C₈ alkyl; C₂ -C₈ alkenyl;or C₆ -C₁₀ aralkyl optionally substituted with halogen or hydroxy; or

R⁶ and R⁷ together with the nitrogen to which they are bound form apiperidine or pyrrolidine ring optionally substituted with halogen,hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkylthio or C₆ -C₁₀ aralkyl.

Specific compounds within the scope of this genus include:

3-(benzylamino)propane-1,1-bisphosphonic acid;

3-(1-pyrrolidino)propane-1,1-bisphosphonic acid;

3-(N-methyl-N-propylamino)propane-1,1-bisphosphonic acid;

3-(N-methyl-N-isobutylamino)propane-1,1-bisphosphonic acid;

3-(alphamethylbenzylamino)propane-1,1-bisphosphonic acid;

3-(1-cyclohexylethylamino)propane-1,1-bisphosphonic acid;

(4-methyl-3-amino)pentane-1.1-bisphosphonic acid;

(4-methyl-3-benzylamino)pentane-1,1-bisphosphonic acid;

3-aminooctane-1,1-bisphosphonic acid;

4-(benzylamino)hexane-1.1-bisphosphonic acid; and

2-(2-pyrrolidino)ethane-1.1-bisphosphonic acid.

The formulae given above are intended to include tautomeric forms of thestructures drawn therein, as well as physically distinguishablemodifications of the compounds which may arise, for example, fromdifferent ways in which the molecules are arranged in a crystal lattice,or from the inability of parts of the molecule to rotate freely inrelation to other parts, or from geometrical isomerism, or formintra-molecular or inter-molecular hydrogen bonding, or otherwise.

The compounds of such formulae can exist in enantiomeric forms. Theinvention includes both individual enantiomers and mixtures of the twoin all proportions.

As is employed herein, the term "hydrocarbyl", whether representing asubstituent on its own or whether it is part of the definition of alarger group (e.g., as in hydrocarbyloxy, hydrocarbyl-S(O)_(m) --, etc.)is intended to include hydrocarbon groups having from 1 to 16 carbonatoms. The term hydrocarbyl therefore includes, for example, C₁ to C₆alkyl including both straight and branched chain isomers (e.g., methyl,ethyl, propyl, isopropyl, sec-hexyl and hexyl); cycloalkyl of 3 to 16carbon atoms (e.g., cyclopropyl, cyclobutyl and cyclohexyl); C₂ to C₁₆alkenyl including for example allyl and crotyl; C₂ to C₁₆ alkynyl (e.g.propynyl); phenyl; phenylalkyl; alkylphenyl, alkenylphenyl,alkynylphenyl, alkylbenzyl, alkenylbenzyl, alkynyl benzyl, naphthyl andthe like.

The term "substituted" when applied to the term "hydrocarbyl" (or to asimilar term unless specifically defined otherwise) is intended toinclude hydrocarbyl groups, as defined above, having one or moresubstituents selected from the group consisting of halogen (i.e.,fluorine, chlorine, bromine, and iodine); C₁ -C₁₀ alkyl, C₁ -C₁₀ alkoxy,C₁ -C₁₀ alkyl-S(O)_(m) --, nitro, cyano, or CF₃ groups. In the abovedefinitions, m is 0, 1 or 2.

Further, when the hydrocarbyl radical is a substituted aryl radical(e.g., phenyl, benzyl or naphthyl), the substituents may include one ormore of the substituents listed in the last foregoing paragraph. Theterm "substituted pyridyl" is intended to include those substituentsdetailed above for substituted aryl radicals.

In addition, unless specified otherwise, the term "alkyl" is intended toinclude straight chain, branched and cycloalkyl compounds. The abovedefinitions the term "halogen" includes fluoro, chloro, bromo and iodogroups. In polyhalogenated groups the halogens may be the same ordifferent.

The compounds of the present invention have been found to be activeherbicides, possessing utility as postemergence herbicides and usefulagainst a wide range of plant species including broadleaf and grassyspecies.

This invention therefore also relates to a method for controllingundesirable vegetation comprising applying to a locus where control ofsuch vegetation is desired subsequent to the emergence of suchvegetation a herbicidally effective amount of a compound as describedherein, together with an inert diluent or carrier suitable for use withherbicides. The terms "herbicide" and "herbicidal" are used herein todenote the inhibitive control or modification of undesired plant growth.Inhibitive control and modification include all deviations from naturaldevelopment such as, for example, total killing, growth retardation,defoliation, desiccation, regulation, stunting, tillering, stimulation,leaf bum and dwarfing. The term "herbicidally effective amount" is usedto denote any amount which achieves such control or modification whenapplied to the undesired plants themselves or to the area in which theseplants are growing. The term "plants" is intended to include germinatedseeds, emerging seedlings and established vegetation, including bothroots and above-ground portions.

The term "agriculturally acceptable salt" is easily determined by one ofordinary skill in the art and includes alkali metal, ammonium,phosphonium, sulfonium salts, organic derivatives thereof, and the like.

The compounds of this invention wherein R¹ is hydrogen and n is 0 maygenerally be prepared by reacting tetraethyl vinylidene bisphosphonatewith an appropriate amine. Such reaction is typically carried out atbetween about 0° and about 100° C. in the presence of a suitablenonreactive solvent, such as acetonitrile, diethyl ether, toluene,tetrahydrofuran, and the like. The ester groups may then be removedusing bromotrimethylsilane or aqueous hydrochloric acid.

Tetraethyl vinylidene bisphosphonate may be prepared in accordance withthe method disclosed by C. Degenhardt et al., J. Org. Chem., Vol 51, pp3488-3490 (1986). The amines employed are either commercially availableor may be prepared by means well known to one of skill in the art, e.g.,preparation from the corresponding bromides by a Gabriel Synthesis (seeVogel, "A Textbook of Practical Organic Chemistry", 3d Ed., pp 569).

The compounds of this invention wherein R¹ is hydrogen and n is not 0may be generally prepared by alkylation of tetraethyl methylenebisphosphonate with a substituted alkyl halide, such as allyl bromide,ethyl bromoacetate or N,N-dimethyl chloroacetamide and subsequentconversion of the olefin, ester or amide to an amine and hydrolysis ofthe phosphonate esters to phosphonic acids.

Alternatively, for compounds where R¹ ═H and n=1, the compounds may beprepared by adding a nitroalkane to vinylidine bisphosphonate. Thisintermediate nitro compound may be reduced to the primary amine fromwhich various substituted amines can be produced by reductivealkylation. On the other hand, the nitro group may be hydrolyzed to givea ketone which can be reductively aminated to give various amines.

For the production of compounds wherein the amine contains sensitivegroups, the phosphonate ester groups may first be transesterified by theuse of a compound such as bromotrimethylsilane. Such groups can besubsequently unblocked by hydrolysis with water.

Alternatively, for producing compounds wherein R¹ is other than H, theappropriate carboxylic acid, amide or nitrile can be converted employingPCl₃ and phosphorous acid or P₂ O₃ utilizing means well known to thoseof skill in the art.

The compositions of this invention comprise a compound of Formula (I)above and a suitable carrier, which carriers are well known to one ofordinary skill in the art.

The compounds of the present invention are useful as herbicides and canbe applied in a variety of ways known to those skilled in the art, atvarious concentrations. The compounds are useful in controlling thegrowth of undesirable vegetation by post-emergent application to thelocus where control is desired. In practice, the compounds are appliedas formulations containing the various adjuvants and carriers known toor used in the industry for facilitating dispersion. The choice offormulation and mode of application for any given compound may affectits activity, and selection will be made accordingly. The compounds ofthe invention may thus be formulated as wettable powders, asemulsifiable concentrates, as powders or dusts, as flowables, assolutions, suspensions or emulsions, or in controlled-release forms suchas microcapsules. These formulations may contain as little as about 0.5%to as much as about 95% or more by weight of active ingredient. Theoptimum amount for any given compound will depend upon the nature ofplants to be controlled. The rate of application will generally varyfrom about 0.01 to about 10 pounds per acre, preferably from about 0.02to about 4 pounds per acre.

Wettable powders are in the form of finely divided particles whichdisperse readily in water or other liquid carriers. The particlescontain the active ingredient retained in a solid matrix. Typical solidmatrices include fuller's earth, kaolin clays, silicas and other readilywettable organic or inorganic solids. Wettable powders normally containabout 5% to about 95% of the active ingredient plus a small amount ofwetting, dispersing, or emulsifying agent.

Emulsifiable concentrates are homogeneous liquid compositionsdispersible in water or other liquid, and may consist entirely of theactive compound with a liquid or solid emulsifying agent, or may alsocontain a liquid carrier, such as xylene, heavy aromatic naphthas,isophorone and other nonvolatile organic solvents. In use, theseconcentrates are dispersed in water or other liquid and normally appliedas a spray to the area to be treated. The amount of active ingredientmay range from about 0.5% to about 95% of the concentrate.

Dusts are free-flowing admixtures of the active ingredient with finelydivided solids such as talc, clays, flours and other organic andinorganic solids which act as dispersants and carriers.

Microcapsules are typically droplets or solutions of the active materialenclosed in an inert porous shell which allows escape of the enclosedmaterial to the surrounds at controlled rates. Encapsulated droplets aretypically about 1 to 50 microns in diameter. The enclosed materialtypically constitutes about 50 to 95% of the weight of the capsule, andmay include solvent in addition to the active compound. Shell ofmembrane materials include natural and synthetic rubbers, cellulosicmaterials, styrene-butadiene copolymers, polyacrylonitriles,polyacrylates, polyesters, polyamides, polyureas, polyurethanes andstarch xanthates.

Other useful formulations for herbicidal applications include simplesolutions of the active ingredient in a solvent in which it iscompletely soluble at the desired concentration, such as water, acetone,alkylated naphthalenes, xylene and other organic solvents. Pressurizedsprayers, wherein the active ingredient is dispersed in finely-dividedform as a result of vaporization of a low boiling dispersant solventcarrier may also be used.

Many of these formulations include wetting, dispersing or emulsifyingagents. Examples are alkyl and alkylaryl sulfonates and sulfates andtheir salts; polyhydric alcohols; polyethoxylated alcohols; esters andfatty amines. These agents when used normally comprise from 0.1% to 15%by weight of the formulation.

Each of the above formulations can be prepared as a package containingthe herbicide together with other ingredients of the formulation(diluents, emulsifiers, surfactants, etc.). The formulations can also beprepared by a tank mix method, in which the ingredients are obtainedseparately and combined at the grower site.

The compounds of the present invention are also useful when combinedwith other herbicides and/or defoliants, desiccants, growth inhibitors,and the like. These other materials can comprise from about 5% to about95% of the active ingredients in the formulations. These combinationsfrequently provide a higher level of effectiveness in controlling weedsand often provide results unattainable with separate formulations of theindividual herbicides.

Examples of other herbicides, defoliants, desiccants and plant growthinhibitors with which the compounds of this invention can be combinedare:

A. Benzo-2,1,3-thiadiazin-4-one-2,2-dioxides such as bentazone;

B. hormone herbicides, particularly the phenoxyalkanoic acids such asMCPA, MCPA-thioethyl, dichlorprop, 2,4,5-T, MCPB, 2,4-D,2,4-DB,mecoprop, trichlopyr, fluroxypyr, clopyralid, and their derivatives(e.g. salts, esters and amides);

C. 1,3-dimethylpyrazole derivatives such as pyrazoxyfen, pyrazolate andbenzofenap;

D. Dinitrophenols and their derivatives (e.g. acetates such as DNOC,dinoterb, dinoseb and its ester, dinoseb acetate;

E. dinitroaniline herbicides such as dinitramine, trifluralin,ethalfluralin, pendimethalin; and oryzalin;

F. arylurea herbicides such as diuron, flumeturon, metoxuron, neburon,isoproturon, chlorotoluron, chloroxuron, linuron, monolinuron,chlorobromuron, daimuron, and methabenzthiazuron;

G. phenylcarbamoyloxyphenylcarbamates such as phenmedipham anddesmedipham;

H. 2-phenylpyridazin-3-ones such as chloridazon, and norflurazon;

I. uracil herbicides such as lenacil, bromacil and termacil;

J. triazine herbicides such as atrazine, simazine, aziprotryne,cyanazine, prometryn, dimethametryn, simetryne, and terbutryn;

K. phosphorothioate herbicides such as piperophos, bensulide, andbutamifos;

L. thiolcarbamate herbicides such as cycloate, vernolate, molinate,thiobencarb, butylate*, EPTC*, triallate, diallate, ethyl esprocarb,tiocarbazil, pyridate, and dimepiperate;

M. 1,2,4-triazin-5-one herbicides such as metamitron and metribuzin;

N. benzoic acid herbicides such as 2,3,6-TBA, dicamba and chloramben;

O. anilide herbicides such as pretilachlor, butachlor, the correspondingalachlor, the corresponding compound propachlor, propanil, metazachlor,metolachlor, acetochlor, and dimethachlor;

P. dihalobenzonitrile herbicides such as dichlobenil, bromoxynil andioxynil;

Q. haloalkanoic herbicides such as dalapon, TCA and salts thereof;

R. Diphenylether herbicides such as lactofen, fluroglycofen or salts oresters thereof, nitrofen, bifenox, acifluorfen and salts and estersthereof, oxyfluorfen and fomesafen; chlornitrofen and chlomethoxyfen;

S. phenoxyphenoxypropionate herbicides such as diclofop and estersthereof such the methyl ester, fluazifop and esters thereof, haloxyfopand esters thereof, quizalofop and esters thereof and fenoxaprop andesters thereof such as the ethyl ester;

T. triketone and cyclohexanedione herbicides such as alloxydim and saltsthereof, sethoxydim, cycloxydim, sulcotrione, tralkoxydim, andclethodim;

U. Sulfonyl urea herbicides such as chlorosulfuron, sulfometuron,metsulfuron and esters thereof; benzsulfuron and esters thereof such asthe ester thereof methyl, DPX-M6313, chlorimuron and esters such as theethyl ester thereof, pirimisulfuron and esters such as the methyl esterthereof, DPX-LS300 and pyrazosulfuron;

V. Imidazolidinone herbicides such as imazaquin, imazamethabenz,imazapyr and isopropylammonium salts thereof, imazathapyr;

W. arylanilide herbicides such as flamprop and esters thereof,benzoylpropethyl, diflufenican;

X. amino acid herbicides such as glyphosate and gluyfosinate and theirsalts and esters, sulphosate, and bilanafos;

Y. organoarsenical herbicides such as MSMA;

Z. herbicidal amide derivative such as napropamide, propyzamide,carbetamide, tebutam, bromobutide, isoxaben, naproanilide, diphenamid,and naptalam;

AA. miscellaneous herbicides including ethofumesate, cinmethylin,difenzoquat and salts thereof such as the methyl sulfate salt,clomazone, oxadiazon, bromofenoxim, barban, tridiphane, (in the ratio3:1) flurochloridone, quinchlorac and mefanacet;

BB. examples of useful contact herbicides include bipyridyliumherbicides such as those in which the active entity is paraquat andthose in which the active entity is diquat. * These compounds arepreferably employed in combination with a safener such as2,2-dichloro-N,N-di-2-propenylacdtamide (dichlormid).

These formulations can be applied to the areas where control is desiredby conventional methods. Dust and liquid compositions, for example, canbe applied by the use of powerdusters, boom and hand sprayers and spraydusters. The formulations can also be applied from airplanes as a dustor a spray or by rope wick applications.

The following are examples of typical formulations:

    ______________________________________                                        5% dust:       5 parts active compound                                                      95 parts talc                                                   2% dust:       2 parts active compound                                                       1 part highly dispersed silicic acid                                         97 parts talc                                                   ______________________________________                                    

These dusts are formed by mixing the components then grinding themixture to the desired particle size.

    ______________________________________                                        Wettable powders:                                                             ______________________________________                                        70%: 70     parts active compound                                                  5      parts sodium dibutylnaphthylsulfonate                                  3      parts naphthalenesulfonic acid/phenolsulfonic acid/phenol-                    sulfonic acid/formaldehyde condensate (3:2: 1)                         10     parts kaolin                                                           12     parts Champagne chalk                                             40%: 40     parts active compound                                                  5      parts sodium lignin sulfonate                                          1      part sodium dibutylnaphthalene sulfonic acid                           54     parts silicic acid                                                25%  25     parts active compound                                                  4.5    parts calcium lignin sulfate                                           1.9    parts Champagne chalk/-hydroxyethyl cellulose (1:1)                    8.3    parts sodium aluminum silicate                                         16.5   parts kieselguhr                                                       46     parts kaolin                                                      10%  10     parts active compound                                                  3      parts of a mixture of sodium salts of saturated                               fatty alcohol sulfates                                                 5      parts naphthalenesulfonic acid/formaldehyde condensate                 82     parts kaolin                                                      ______________________________________                                    

These wettable powders are prepared by intimately mixing the activecompounds with the additives in suitable mixers, and grinding theresulting mixture in mills or rollers.

    ______________________________________                                        Emulsifiable concentrate:                                                     ______________________________________                                        25%    25     parts active substance                                                 2.5    parts epoxidized vegetable oil                                         10     parts of an akylarylsulfonate/fatty alcohol polyglycol                        ether mixture                                                          57.5   parts xylene                                                    ______________________________________                                    

The amount of the present compositions which constitute a herbicidallyeffective amount depends upon the nature of the seeds or plants to becontrolled. The rate of application of active ingredients varies fromabout 0.01 to about 25 pounds per acre, preferably about 0.10 to about10 pounds per acre with the actual amount depending on the overall costsand the desired results. It will be readily apparent to one skilled inthe art that compositions exhibiting lower herbicidal activity willrequire a higher dosage than more active compounds for the same degreeof control.

EXAMPLES

The following examples are intended to further illustrate the presentinvention and are not intended to limit the scope of this invention inany manner whatsoever.

Example 1 Preparation of 2- 1-(1,2,4-triazole)!ethane-1,1-bisphosphonicacid (Compound No. 3)

One gram of 1,2,4-triazole was dissolved in 40 ml of THF and cooled to-78° C. in a nitrogen atmosphere. n-Butyl-lithium (974 mg) was thenadded dropwise and the resultant white suspension stirred at -78° C. forfive minutes. After warming to room temperature, the mixture was stirredfor 45 minutes and then cooled again to -78° C. Tetraethylvinylidinebiphosphonate (4.78 gm) was then added dropwise over a 20minute period. When the addition was complete, the mixture was stirredfor 15 minutes at -78° C., then warmed to 0° C. and stirring continuedfor one hour. The reaction was quenched with 10 ml of water and the THFremoved under reduced pressure to give the crude product which was thencombined with 35 ml of aqueous K₂ CO₃ solution. The resulting mixturewas extracted with 3×100 ml portions of dichloromethane. The extractswere combined, dried (MgSO₄), and the solvent removed under reducedpressure to afford a mobile oil. Column chromatography on silica gelwith 10% methanol/dichloromethane provided 1.3 gm of tetraethyl 2-1-(1,2,4-triazole)ethane-1,1-bisphosphonate. Hydrolysis of this materialto form Compound No. 3 was achieved by heating a dichloromethanesolution of the tetraethyl ester and 500 mol% of bromotrimethylsilane at45° C. for four hours and then removing the volatiles in vacuo.Refluxing the residual oil with water for 30 minutes followed by coolingto room temperature and removal of the water under high vacuum resultedin the isolation of Compound No. 3 in quantitative yield.

Example 2 Preparation of1-hydroxy-(2-amino-2-methyl)propane-1,1-bisphosphonic acid (Compound No.8)

To a three-necked 250 ml round-bottomed flask equipped with a condenser,mechanical stirrer, oil bath and thermometer were added 2.37 gm of2-aminoisobutyric acid, 85 ml of chlorobenzene and 3.2 gm of phosphorousacid. The mixture was heated at reflux for one hour and then cooled to50° C. Phosphorus trichloride (9.62 gm) was then added and the mixtureagain heated to refluxing with stirring for five hours. At the end ofthis time, the mixture was allowed to cool to room temperature and thechlorobenzene carefully decanted. Fresh chlorobenzene (85 ml) and 80 mlof 6N HCl were then added and the mixture heated to refluxing withstirring. After six hours, the yellowish suspension was cooled to roomtemperature, vacuum filtered through dicalite, and the volatiles removedunder high vacuum to afford a colorless syrup. Trituration with ethanolunder steam heating provided 3.09 gm of Compound No. 8 as a white solidafter isolation by vacuum filtration.

Example 3 Preparation of 1-hydroxy-1-(2-pyrrolidino)-1,1-bisphosphonicacid (Compound No. 9)

To a 200 ml three-necked flask equipped with a mechanical stirrer andreflux condenser carrying a nitrogen bubbler were added 4 gm of proline;5.7 gm. of phosphorous acid and 25 ml of dioxane. Phosphorus trichloride(9.6 gm) was then added dropwise at 80° C. and the mixture stirred at80° C. for two hours. After cooling the reaction mixture to roomtemperature, water (150 ml) was added and the resulting mixture wasfiltered through activated carbon. The filtrate was evaporated underreduced pressure and the residual clear oil placed in a vacuum oven (60°C.) overnight. At the end of this time the residue was triturated withEtOH and the resulting white solid isolated by vacuum filtration. Dryingthe solid in a vacuum oven at 60° C. afforded 5.9 gm. of Compound No. 9.

Example 4 Preparation of 2-(but-3-enylamino)ethane-1,1-bisphosphonicacid (Compound No. 29)

A solution of 1.08 gm of 1-aminobut-3-ene in five ml of methanol wasadded to 3.8 gm of tetraethyl vinylidinebisphosphonate at roomtemperature. After the resulting mixture had stirred overnight, anadditional 0.12 gm. of 1-aminobut-3-ene was added and the stirringcontinued for an additional four hours. The reaction mixture was thenconcentrated under reduced pressure to yield 4.56 gm of tetraethyl2-(but-3-enylamino)ethane-1,1-bisphosphonate. A 4.4 gm sample of thismaterial was combined with five ml of acetonitrile and 7.2 ml ofbromotrimethylsilane. After stirring at room temperature for 48 hours,the solution was heated to refluxing for four hours and thenconcentrated under reduced pressure. The resulting tetra(trimethylsilyl)ester was hydrolyzed by refluxing with 25 ml of water for 30 minutes.Removal of the volatile materials by lyophylization afforded 3.2 gm ofCompound No. 29 as a stiff, colorless, hygroscopic foam.

Example 5 Preparation of2-(3-methyl-1-piperidinyl)ethane-1,1-bisphosphonic acid (Compound No.37)

A solution of one ml of 3-methylpiperidine in five ml of methanol wasadded dropwise to 2.43 gm of tetraethyl vinylidinebisphosphonate at roomtemperature. The reaction was stirred overnight and the mixture thenconcentrated under reduced pressure to yield 3.4 grams of tetraethyl2-(3-methyl-1-piperidinyl)ethane-1,1-bisphosphonate. A portion of thismaterial (3.37 gm) was dissolved in five ml of acetonitrile followed bythe addition of five ml of bromotrimethylsilane. The resulting mixturewas refluxed overnight, then allowed to cool to room temperature, andthen concentrated under reduced pressure. Water (25 ml) was added to theresidual oil and the mixture stirred for three hours. Removal of thewater and other volatile components under high vacuum afforded 2.84 gmof Compound No. 37 as a stiff, hygroscopic, colorless foam.

Example 6 Preparation of 2-(4 methylbenzylamino)ethane-1,1-bisphosphonicacid (Compound No. 66)

To a 100 ml boiling flask were added 3.5 gm of tetraethylvinylidine-1,1-bisphosphonate, 20 ml of acetonitrile, and 1.5 gm of4-methylbenzylamine. The resulting mixture was magnetically stirredovernight at room temperature. At the end of this time, the solvent wasremoved under reduced pressure to give 4.66 gm of tetraethyl2-(4-methylbenzylamino)ethane-1,1-bisphosphonate. A portion of thismaterial (3.87 gm) was placed in a 100 ml boiling flask equipped with amagnetic stirrer and refluxed for four hours with 25 ml of concentratedHCl. Removal of the volatile materials under high vacuum afforded 3.21gm of Compound No. 67 as a colorless, hygroscopic glass.

Example 7 Preparation of 3-(dipropylamino)propane-1,1-bisphosphonic acid(Compound No. 155)

A. Preparation of 3,3-bis(diethoxylphosphinyl)-propanoic acid

A solution of NaOH (4.00 g, 100 mmol) in water (50 ml) was added to asolution of ethyl 3,3-bis(diethoxyphosphinyl)propionate (32.6 g, 87mmol) in EtOH (100 ml), and heated at 80° C. for 1 hour. After cooling,the EtOH was evaporated, and the residue was acidified to methyl orangewith 12N HCl. The product was extracted into dichloromethane (5×50 ml).The organic layer was dried (Na₂ SO₄) and concentrated to give the titlecompound (28.8 g, 96%) as a viscous oil.

B. Preparation of N,N-dipropyl-3,3-bis(diethoxy-phosphinyl)propionamide

To a solution of 3,3-bis(diethoxyphosphinyl)-propanoic acid (1.5 g, 4.34mmol) and dimethylformamide (2 drops) in dichloromethane (10 ml) wasadded oxalyl chloride (0.61 g., 4.77 mmol). The solution was stirred atambient temperature until gas evolution ceased (˜1 hour). The solutionwas evaporated and pumped under vacuum to give the acid chloride as anorange oil, which was used directly.

The acid chloride from above was dissolved in dichloromethane (20 ml)and cooled to 0° C. A solution of dipropylamine (0.89 g, 8.8 mmol) indichloromethane (5 ml) was added dropwise, allowed to warm to roomtemperature, and stirred for 18 hours. Dichloromethane (25 ml) was addedand the reaction mixture washed with 1N HCl (25 ml) and NaHCO₃ (25 ml).The organic layer was dried (Na₂ SO₄) and concentrated to give the titlecompound (1.3 g, 70%) as an oil.

C. Preparation oftetraethyl-3-(dipropylamino)-propane-1,1-bisphosphonate

A solution of N,N-dipropyl-3,3-bis(diethoxyphosphinyl)propionamide (1.25g, 2.9 mmol) in THF (7.1 ml) was cooled to 0° C., andborane-methylsulfide (0.71 ml, 7.1 mmol) was added via syringe. Thereaction was stirred at 0° C. for 20 minutes, then warmed at 65 C. for 3hours. The reaction mixture was cooled to 0° C. and 6N HCl (6 ml) wasadded carefully. The solvent was removed m vacuo, and the residue wastreated with methanol (5 ml) and concentrated. The residue was dissolvedin water (10 ml) and extracted with Et₂ O (3×10 ml). The aqueous layerwas made basic to phenolphthalein with solid KOH and saturated withNaCl. The product was extracted into dichloromethane (5×20 ml), dried(Na₂ SO₄) and concentrated to give the title compound (0.71 g, 60%).

D. Preparation of 3-(dipropylaminopropane-1,1-bisphosphonic acid

Tetraethyl 3-(dipropylamino)propane-1,1-bisphosphonate (0.55 g, 1.3mmol) and 12NHCl (6 ml) were heated at reflux for 20 hours. Aftercooling, the volatile materials were removed under vacuum to give 0.47 gof Compound No. 155 as a hygroscopic glass.

Example 8 Preparation of 3-(benzylamino)pentane-1,1-bisphosphonic acid(Compound No. 159)

A. Preparation ofN-methoxy-N-methyl-3,3-bis-(diethoxyphosphinyl)propionamide.

To a solution of 3,3-bis(diethoxyphosphinyl)propanoic acid (4.00 g, 11.5mmol) and dimethylformamide (2 drops) in dichloromethane (25 ml) wasadded oxalyl chloride (1.65 g, 13.0 mmol). The solution was stirred atambient temperature until gas evolution ceased (˜1 hour). The solutionwas evaporated and benzene (20 ml) was added. The solvent was removedunder vacuum to give the acid chloride as an orange oil, which was useddirectly. The acid chloride from above was dissolved in dichloromethane(100 ml) and N-methyl-O-methylhydroxylamine hydrochloride (1.25 g, 13.0mmol) was added. The reaction mixture was cooled in an ice bath andpyridine (2.05 g, 26.0 mmol) was added dropwise. After the addition, thereaction mixture was allowed to warm to room temperature for 1 hour.This mixture was washed with 1N HCl (50 ml) and saturated NaHCO₃ (50ml), dried (Na₂ SO₄) and concentrated to give the crude product as anoil. Flash chromatography on silica gel eluting with 20% i-propanol inEtOAc gave the title compound (3.50 g, 78%) as a light yellow oil.

B. Preparation of tetraethyl 3-oxopentane-1,1-bisphosphonate

A solution of N-methoxy-N-methyl-3,3-bis(diethoxyphosphinyl)propionamide(1.00 g, 2.6 mmol) in THF (5 ml) was slowly added to a slurry of 80%sodium hydride (80 mg, 2.7 mmol) in THF (10 ml) at 0° C. Stirring wascontinued until all of the hydride was consumed (˜20 minutes). Thesolution was cooled to -78° C. and ethylmagnesium bromide (1.0 ml of a3.0M solution in diethyl ether, 3.0 mmol) was added. After the addition,the reaction mixture was warmed to 0° C. and stirred for one hour. Thereaction was quenched by pouring slowly into a well-stirred ice-coldmixture of ethanol (40 ml) and concentrated HCl (5 ml). The solventswere removed in vacuo, the residue was taken up in brine (20 ml) andextracted with dichloromethane (4×20 ml). The combined extracts weredried (Na₂ SO₄), concentrated in vacuo, and the resulting oil waspurified by flash chromatography on silica gel eluting with 10%i-propanol in ethyl acetate to give the title compound (0.50 g, 54%) asa pale yellow oil.

C. Preparation of 3-(benzylamino)pentane-1,1-bisphosphonic acid

To a stirred solution of tetraethyl 3-oxopentane-1,1-bisphosphonate(0.50 g, 1.4 mmol) in methanol (5 ml) was added a small amount ofbromothymol blue and benzylamine (0.75 g, 7.0 mmol). Acetic acid wasadded dropwise until the solution turned yellow (pH=6), and NaCNBH₃ (57mg, 0.9 mmol) was added. The resulting yellow solution was stirred atroom temperature for 2 days, at which time more NaCNBH₃ (20 mg) wasadded. After stirring a total of 4 days, the reaction was quenched byadding concentrated HCl until the pH was less than 1, and the solventswere removed in vacuo. The residue was taken up in water (10 ml) andwashed with diethyl ether (2×20 ml). The aqueous layer was made basic(pH greater than 10) by the addition of solid KOH, saturated with NaCl,and extracted with dichloromethane (5×25 ml). The combined extracts weredried (Na₂ SO₄) and concentrated to give tetraethyl3-benzylaminopentane-1,1-bisphosphonate. This material was hydrolyzed byheating at reflux in concentrated HCl (6 ml) for 20 hours. The volatileswere removed under vacuum, the residue dissolved in water (10 ml) andconcentrated under vacuum to give 0.49 g of Compound No. 159 as ahygroscopic foam.

Example 9 Preparation of 3-(butylamino)propane-1,1-bisphosphonic acid(Compound No. 158)

A. Preparation of N-butyl-3,3-bis(diethoxyphosphinyl)propionamide

Tetraethyl methylenebisphosphonate (1.44 g, 5.0 mmol) in THF (1 mL) wasadded to a slurry of 80% sodium hydride (150 mg, 5.0 mmol) in THF (4 mL)at 0° C. The reaction was warmed to room temperature and stirred untilall of the hydride was consumed. A solution of N-butyl-2-chloroacetamide(0.75 g, 5.0 mmol) in THF (1 ml) and potassium iodide (100 mg) were thenadded. The reaction mixture was then heated at 50° C. for 18 hours,during which time sodium chloride precipitated. Additional sodiumhydride (20 mg) was added, and the reaction mixture was heated anadditional 4 hours. After cooling, the mixture was poured into 1N HCl(10 mL) and diethyl ether (50 mL) was added. The diethyl ether layer wasfurther extracted with water (3×10 mL). The combined aqueous fractionswere extracted with dichloromethane (4×25 mL). The combined extractswere dried (Na₂ SO₄) and concentrated to give the title compound (1.40g, 70%) as an oil.

B. Preparation of 3-(butylamino)propane-1,1-bisphosphonic acid

A solution of N-butyl-3,3-bis(diethoxyphosphinyl)propionamide (1.40 g,3.5 mmol) in THF (9 mL) was cooled to 0° C., and borane-methyl sulfide(0.90 ml, 9.0 mmol) was added via syringe. The reaction was stirred at0° C. for 5 minutes, then warmed to 65° C. for 3 hours. The reactionmixture was cooled to 0° C. and 6N HCl (6 ml) was added carefully. Thesolvent was removed in vacuo, and the residue was repeatedlyconcentrated from methanol (3×10 mL). The product was dissolved in 12NHCl and heated at reflux for 20 hours. After cooling, the volatilematerials were removed under vacuum, the residue was dissolved in water(10 mL) and then concentrated to give 1.05 g of Compound No. 158 as ahygroscopic glass.

Example 10 Preparation of 2-(2-pyrrolidino)ethane-1,1-bisphosphonicacid, triammonium salt (Compound No. 245)

A. Preparation of tetraethyl 2 2-(1-pyrrolino)!ethane-1,1-bisphosphonate

A solution of N-methoxy-N-methyl-3,3-bis(diethoxyphosphinyl)propionamide(1.82 g, 4.7 mmol) in THF (5 ml) was slowly added to a slurry of 80%sodium hydride (160 mg, 5.3 mmol) in THF (15 ml) at 0° C. Stirring wascontinued until all of the hydride was consumed (˜20 minutes). Thesolution was cooled to 0° C. and 3-1-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)!propylmagnesiumbromide (15 ml of a 1.0M solution in diethyl ether, 15 mmol) was added.After the addition, the reaction mixture was allowed to warm to roomtemperature and stirred for 15 hours. At that time, the mixture wascooled to 0° C. and quenched by the slow addition of 10% HCl, andstirred at room temperature for 2 hours. Ether (30 mL) was added and theproduct was extracted with 1N HCl (3×10 mL). The combined aqueousextracts were washed with ether (10 mL) and then solid KOH was added tobring the pH to 10. The solvent was evaporated and the residue extractedwith dichloromethane (4×50 mL). Evaporation of the solvent gave thecrude product which was purified by flash chromatography on silica geleluting with 5% methanol in chloroform to give the title compound (0.40g).

B. Preparation of tetraethyl 2-(2-pyrrolidino)ethane-1,1-bisphosphonate

Tetraethyl 2- 2-(1-pyrrolino)!ethane-1,1-bisphosphonate (0.40 g, 1.15mmol) was dissolved in ethanol (4 mL) and NaCNBH₃ (80 mg, 1.25 mmol) wasadded. 6N HCl was added to keep the solution acidic to bromocresol green(pH˜4). After 30 minutes, 6N HCl was added (2 mL) and the solvent wasremoved in vacuo. Methanol (10 ml) was added and evaporated. The residuewas added to dichloromethane (20 mL) and extracted into 1N HCl (2×10mL). The solution was made basic (pH˜10) with solid KOH and the productwas extracted into dichloromethane (3×20 ml). The combined organicextracts were dried (K₂ CO₃) and concentrated to give 0.26 g oftetraethyl 2-(2-pyrrolidino)ethane-1,1-bisphosphonate.

C. Preparation of 2-(2-pyrrolidino)ethane-1,1-bisphosphonic acid,triammonium salt

To a stirred solution of tetraethyl2-(2-pyrrolidino)ethane-1,1-bisphosphonate (0.26 g, 0.75 mmol) in drydichloromethane (0.5 mL) at 0° C. was added bromotrimethylsilane (1.00mL, 8.0 mmol), and the solution was allowed to warm to room temperature.After stirring for 16 hours, the solvent was removed in vacuo, theresidue was dissolved in benzene (7 mL) and concentrated in vacuo. Tothe residue was added NH₄ OH (4 mL of a 3.5M solution) which was stirredfor 30 minutes at room temperature. The solvent was removed in vacuo,and the residue concentrated repeatedly from methanol (2×5 mL) to give0.24 g of 2-(2-pyrrolidino)ethane-1,1-bisphosphonic acid as a whitepowder.

Example 11 Preparation of 5-aminopentane-1,1-bisphosphonic acid,triammonium salt (Compound No. 249)

A. Preparation of tetraethyl 5-aminopentane-1,1-bisphosphonate

Tetraethyl vinylidine bisphosphonate (1.20 g, 4.0 mmol) was dissolved indry THF (10 mL) and cooled to 0° C. A solution of 3-1-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)!propylmagnesiumbromide in ether (4.5 mL of 1.0M solution, 4.5 mmol) was added slowlyand the reaction mixture was then allowed to warm to room temperaturefor 15 hours. The reaction was quenched with 1N HCl (25 mL) and stirredfor 2 hours. This was washed with ether (10 mL). The ether layer wasextracted with 1N HCl and the combined aqueous extracts were made basic(pH=10) with solid KOH. Volatiles were removed m vacuo, and the residuewas extracted with dichloromethane (3×50 mL). The solution wasconcentrated to 20 mL and extracted with 1N HCl (2×10 mL). Solid KOH wasadded to pH=10, and the product was extracted into dichloromethane (3×15mL). The solution was dried (K₂ CO₃) and concentrated to give the titlecompound (0.54 g) as an oil.

B. Preparation of 5-aminopentane-1,1-bisphosphonic acid, triammoniumsalt

To a stirred solution of tetraethyl 5-aminopentane-1,1-bisphosphonate(0.51 g, 1.5 mmol) in dry dichloromethane (0.5 mL) at 0° C. was addedbromotrimethylsilane (1.3 mL, 10 mmol), and the solution was allowed towarm to room temperature. After stirring for 16 hours, the solvent wasremoved in vacuo, the residue was dissolved in benzene (5 mL) andconcentrated in vacuo. To the residue was added NH₄ OH (7 mL of a 3.0Msolution) which was stirred for 30 minutes at room temperature. Thesolvent was removed in vacuo, and the residue concentrated repeatedlyfrom methanol (2×5 mL) to give 0.52 g of 5-amino-1,1-pentylbisphosphonicacid, triammonium salt as a white powder.

Example 12 Preparation of N-benzyl-5-aminopentane-1,1-bisphosphonicacid, triammonium salt (Compound No. 250)

A. Preparation of tetraethyl N-benzoyl-5-aminopentane-1,1-bisphosphonate

A solution of benzoyl chloride (0.73 g, 5.0 mmol) in dichloromethane wasadded slowly to a solution of tetraethyl5-aminopentane-1,1-bisphosphonate (1.50 g, 4.5 mmol) from Example 11,part A, and triethylamine (0.76 mL, 5.5 mmol) in dichloromethane at 0°C. After warming to room temperature for 30 minutes, the reaction wasquenched by addition of 1N HCl (30 mL). The product was extracted intodichloromethane (2×20 mL) and the combined organic layers were washedwith saturated NaHCO₃ (2×15 mL), dried (Na₂ SO₄), and concentrated invacuo. Flash chromatography on silica gel eluting with 15% i-propanol inethylacetate in EtOAc gave the title compound (0.64 g) as an oil.

B. Preparation of tetraethyl N-benzyl-5-aminopentane-1,1-bisphosphonate

A solution of tetraethyl N-benzoyl-5-aminopentane-1,1-bisphosphonate(0.63 g, 1.36 mmol) in THF (3.4 mL) was cooled to 0° C., and boranemethylsulfide (0.34 ml, 3.4 mmol) was added via syringe. The reactionwas stirred at 0° C. for 20 minutes, then warmed to 65° C. for 2.5hours. The reaction mixture was cooled to 0° C. and 6N HCl (4.0 ml) wasadded carefully. The solvent was removed in vacuo, and the residue wasconcentrated repeatedly from methanol (2×5 mL). The residue wasdissolved in water (10 ml) and extracted with diethyl ether (3×5 ml).The aqueous layer was made basic to phenolphthalein with solid KOH andsaturated with NaCl. The product was extracted into dichloromethane(5×20 ml), dried (Na₂ SO₄) and concentrated to give the title compound(0.28 g).

C. Preparation of N-benzyl-5-aminopentane-1,1-bisphosphonic acid,triammonium salt

Bromotrimethylsilane (0.54 mL, 4.1 mmol) was added to a stirred solutionof the compound of part B (0.26 g, 0.58 mmol) in dry dichloromethane(0.5 mL) at 0° C., and the solution was allowed to warm to roomtemperature. After stirring for 18 hours, the solvent was removed invacuo. To the residue was added NH₄ OH (7 mL of a 3.0M solution) whichwas stirred for 30 minutes at room temperature. The solvent was removedin vacuo, and the residue concentrated repeatedly from methanol (2×5 mL)to give 0.32 g N-benzyl-5-aminopentane-1,1-bisphosphonic acid,triammonium salt as a white powder.

Example 13 Preparation of 3-aminooctane-1,1-bisphosphonic acid (CompoundNo. 258)

A. Preparation of tetraethyl 3-nitrooctane-1,1-bisphosphonate

A solution of tetraethyl vinvylidinebisphosphonate (2.0 g, 6.67 mmol) inTHF (3 ml) was added dropwise to a stirred solution of 1-nitrohexane(0.87 g, 6.67 mmol) and diisopropylamine (0.76 g, 7.50 mmol) in THF (4mL) at room temperature. The reaction mixture was stirred at ambienttemperature for 18 hours, and then heated at 50° C. for 3 hours. Aftercooling, the solvent was removed m vacuo. The residue was dissolved indichloromethane (30 mL) and washed with 1N HCl (10 mL) and water (10mL). The combined aqueous layers were extracted with dichloromethane (10mL). The organic layers were pooled, dried (Na₂ SO₄) and concentrated.Flash chromatography on silica gel eluting with 5% methanol inchloroform gave the title compound (2.3 g, 80%) as an oil.

B. Preparation of tetraethyl 3-aminooctane-1,1-bisphosphonate

To a stirred solution of tetraethyl 3-nitrooctane-1,1-bisphosphonate(0.70 g, 1.62 mmol) in methanol (4 mL) was added ammonium formate (0.45g, 6.9 mmol) and 10% palladium on carbon (0.070 g). After 24 hours, more10% palladium on carbon (0.035 g) and ammonium formate (0.45 g, 6.9mmol) were added. After stirring for a total of 4 days, the reactionmixture was filtered, rinsing the residue with methanol, andconcentrated. The residue was taken up in brine (5 mL) and extractedwith dichloromethane (4×15 mL), dried (Na₂ SO₄) and concentrated to givethe title compound (0.60 g, 95%) as an oil.

C. Preparation of 3-aminooctyl-1,1-bisphosphonic acid, triammonium salt

To a solution of tetraethyl 3-aminooctane-1,1-bisphosphonate (0.45 g,1.12 mmol) in dry dichloromethane (1.1 mL) was addedbromotrimethylsilane (1.05 mL, 7.85 mmol) via syringe. After 18 hours,the mixture was concentrated under vacuum. To the residue was added 3NNH₄ OH (8 mL) which was stirred for 30 minutes at room temperature. Thesolvent was removed in vacuo and the residue concentrated from methanol(2 mL) to give 0.40 g of 3-aminooctane-1,1-bisphosphonic acid,triammonium salt as a white powder.

Employing a process similar to those described above, the followingcompounds, listed in Tables I-V, were prepared:

                                      TABLE I                                     __________________________________________________________________________     ##STR14##                                                                    Comp.                                                                         No.  R.sup.1                                                                           R.sup.4                                                                           R.sup.5                                                                           R.sup.6  R.sup.7                                             __________________________________________________________________________     1   H   H   H   H        Phenyl Ph!                                           2   H   H   H   H        2-pyridyl                                            8*  OH  CH.sub.3                                                                          CH.sub.3                                                                          H        H                                                    12  H   H   H   H                                                            nC.sub.3 H.sub.7                                                               14  H   H   H   H        cyclohexyl                                           15  H   H   H   H                                                            iC.sub.3 H.sub.7                                                               16  H   H   H   H                                                            tC.sub.4 H.sub.9                                                               18  H   H   H   CH.sub.3 CH.sub.3                                             22  H   H   H   H                                                            iC.sub.4 H.sub.9                                                               23  H   H   H   C.sub.2 H.sub.5                                                                        C.sub.2 H.sub.5                                      24**                                                                              H   H   H   H                                                            nC.sub.3 H.sub.7                                                               25***                                                                             H   H   H   H                                                            nC.sub.3 H.sub.7                                                               27  H   H   H   H                                                            nC.sub.4 H.sub.9                                                               28  H   H   H   H        OCH.sub.3                                            29  H   H   H   H        CH.sub.2 CH.sub.2 CHCH.sub.2                         30  H   H   H   H                                                            nC.sub.6 H.sub.13                                                              31  H   H   H   H        benzyl                                               32  H   H   H   H        CH.sub.2 CHCH.sub.2                                  33  H   H   H                                                                nC.sub.3 H.sub.7                                                              nC.sub.3 H.sub.7                                                               34  H   H   H   CH.sub.3 OCH.sub.3                                            35  H   H   H   CH.sub.3 OH                                                   36  H   H   H   H        C.sub.2 H.sub.5                                      38  H   H   H   H        CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                   39  OH  H   H   H        CH.sub.3                                             40  H   H   H                                                                nC.sub.4 H.sub.9                                                              nC.sub.4 H.sub.9                                                               41***                                                                             H   H   H   H                                                            nC.sub.6 H.sub.13                                                              42  H   H   H   H                                                                                       ##STR15##                                           43  H   H   H   H                                                                                       ##STR16##                                           44  H   H   H   H                                                                                       ##STR17##                                           45  H   H   H   H        2-methylbenzyl                                       46  H   H   H   H        3-methylbenzyl                                       47  H   H   H   H        CH.sub.2 CH.sub.2 -Ph                                50  H   H   H   H        3-methylpyrid-2-yl                                   51  H   H   H   CH.sub.3                                                     nC.sub.3 H.sub.7                                                               52  H   H   H   CH.sub.3                                                     iC.sub.3 H.sub.7                                                               54  H   H   H   H                                                                                       ##STR18##                                           56  H   H   H   H        2,6-dichloro-4-trifluoromethylanilino                57  H   H   H   CH.sub.2 CHCH.sub.2                                                                    CH.sub.2 CHCH.sub.2                                  58  H   H   H   H        CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                 60  H   H   H   H                                                            nC.sub.3 H.sub.7                                                               61  H   H   H   H        CH.sub.2 CF.sub.3                                    62  H   H   H   C.sub.2 H.sub.5                                                                        CH.sub.2 CHCH.sub.2                                  63  H   H   H   CH.sub.3 CH.sub.2 CHCH.sub.2                                  64  H   H   H   H        cyclopropyl                                          66  H   H   H   H        4-methylbenzyl                                       67  H   H   H   H        4-chlorobenzyl                                       68  H   H   H   H        3-chlorobenzyl                                       69  H   H   H   H        2-chlorobenzyl                                       70  H   H   H   H                                                                                       ##STR19##                                           72  H   H   H   H                                                                                       ##STR20##                                           74  H   H   H   H                                                                                       ##STR21##                                           75  H   H   H   H                                                                                       ##STR22##                                           76  H   H   H   H        2,3-dimethylbenzyl                                   77  H   H   H   H        2,5-dimethylbenzyl                                   78  H   H   H   H        2,4-dimethylbenzyl                                   79  H   H   H   H        3,4-dimethylbenzyl                                   80  H   H   H   H        2-methylcyclopentyl                                  81  H   H   H   H        CH.sub.2 CHCHCH.sub.3                                82  H   H   H   H        CH(C.sub.2 H.sub.5).sub.2                            83  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 Cl                        85  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH(CH.sub.3).sub.2                                               86  H   H   H                                                                nC.sub.3 H.sub.7                                                              nC.sub.4 H.sub.9                                                               88  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 COOH                                                    89  H   H   H   H        CH.sub.2 CH.sub.2 CH-Ph                              90  H   H   H   H                                                                                       ##STR23##                                           93  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 COOH                                                             95  H   H   H                                                                nC.sub.3 H.sub.7                                                              nC.sub.6 H.sub.13                                                              98  H   H   H   H                                                                                       ##STR24##                                           99  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                     102  H   H   H                                                                nC.sub.3 H.sub.7                                                              nC.sub.5 H.sub.11                                                             103  H   H   H   H                                                                                       ##STR25##                                          104  H   H   H   H        4-fluorobenzyl                                      105  H   H   H   H        3,4-difluorobenzyl                                  106  H   H   H   H        2,6-difluorobenzyl                                  107  H   H   H   H        2-fluoro-6-chlorobenzyl                             108  H   H   H   H        2,6-dichlorobenzyl                                  111  H   H   H                                                                nC.sub.3 H.sub.7                                                              nC.sub.10 H.sub.21                                                            118  H   H   H   H        CH(CH.sub.3)CH.sub.2 CH.sub.3                       120  H   H   H   H        2-pyridylmethyl                                     121  H   H   H   H        3-pyridylmethyl                                     122  H   H   H   H        4-pyridylmethyl                                     123  H   H   H   H        2-methoxybenzyl                                     124  H   H   H   CH.sub.3 C.sub.2 H.sub.5                                     125  H   H   H   H                                                                                       ##STR26##                                          131* H   H   H   H        CH.sub.2 CH(OH)CH.sub.3                             132****                                                                            H   H   H   H        CH.sub.2 CH(OH)CH.sub.3                             133***                                                                             H   H   H   H        CH.sub.2 CH(OH)CH.sub.3                             134* H   H   H   H                                                                                       ##STR27##                                          135  H   H   H   H                                                                                       ##STR28##                                          136* H   H   H   H                                                                                       ##STR29##                                          137***                                                                             H   H   H   H                                                                                       ##STR30##                                          138****                                                                            H   H   H   H                                                                                       ##STR31##                                          267  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -Ph             269  H   H   H   H                                                                                       ##STR32##                                          270  H   H   H   CH.sub.3 benzyl                                              271  H   H   H   C.sub.2 H.sub.5                                                                        benzyl                                              272  H   H   H   iC.sub.3 H.sub.7                                                                       benzyl                                              273  H   H   H                                                                nC.sub.4 H.sub.9                                                                   benzyl                                                                   274  H   H   H                                                                nC.sub.3 H.sub.7                                                                   benzyl                                                                   276  H   H   H                                                                iC.sub.4 H.sub.9                                                              sC.sub.4 H.sub.9                                                              277  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 S-Ph            279  H   H   H   H        CH.sub.2 CH(CH.sub.3)-Ph                            280  H   H   H   H        4-methoxybenzyl                                     281  H   H   H   H                                                                                       ##STR33##                                          282  H   H   H   H                                                                                       ##STR34##                                          284  H   H   H   H        CH(CH.sub.3)CH.sub.2 CH.sub.2 -Ph                   286  H   H   H   H                                                                                       ##STR35##                                          287  H   H   H   H                                                                                       ##STR36##                                          289  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 -Ph                                                    290  H   H   H                                                                nC.sub.3 H.sub.7                                                                    ##STR37##                                                               292  H   H   H   H                                                                                       ##STR38##                                          294  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 OH                       295  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OH              296  H   H   H   H                                                                                       ##STR39##                                          297  H   H   H   H                                                                                       ##STR40##                                          298  H   H   H   H                                                                                       ##STR41##                                          299  H   H   H   H        N(CH.sub.3)-Ph                                      303  H   H   H   H        CH(CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.2 -Ph          304  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -Ph                         308  H   H   H                                                                nC.sub.3 H.sub.7                                                              iC.sub.4 H.sub.9                                                              309  H   H   H   H        CH.sub.3                                            311  H   H   H   H        CH.sub.2 CH.sub.2 OH                                312  H   H   H   H                                                                                       ##STR42##                                          313  H   H   H   CH.sub.3                                                     iC.sub.4 H.sub.9                                                              314  H   H   H   H        CH.sub.2 CHCH-Ph                                    315  H   H   H   H        N(CH.sub.3).sub.2                                   317  H   H   H   H        CH.sub.2 CH.sub.2 SCH.sub.2 CH.sub.3                318  H   H   H   H                                                                                       ##STR43##                                          319  H   H   H   H        CH.sub.2 CH.sub.2 OCH.sub.3                         320  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3                323  H   H   H   H        CH.sub.2 CH.sub.2 SCH.sub.3                         324  H   H   H   H        CH.sub.2 CH.sub.2 CH(CH.sub.3)-Ph                   326  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3                327  H   H   H   H                                                            nC.sub.5 H.sub.11                                                             329  H   H   H   H        CH.sub.2 CH(CH.sub.3)CH.sub.2 -Ph                   330  H   H   H   H                                                                                       ##STR44##                                          331  H   H   H   H                                                                                       ##STR45##                                          332  H   H   H   H                                                                                       ##STR46##                                          333  H   H   H   H                                                                                       ##STR47##                                          334  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH(CH.sub.3)-Ph          335  H   H   H   cyclopropyl                                                  nC.sub.3 H.sub.7                                                              336  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  CH.sub.2 -Ph                                        337  H   H   H   CH.sub.3 CH.sub.2 CH.sub.2 CH.sub.2 -Ph                      338  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  CH.sub.2 CH.sub.2 -Ph                               341  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  O-Ph                                                343  H   H   H   H        CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                 344  H   H   H   C.sub.2 H.sub.5                                                                        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -Ph             345  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2        346  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  -Ph                                                 347  H   H   H   C.sub.2 H.sub.5                                                                        CH.sub.2 CH.sub.2 CH.sub.2 -Ph                      348  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.3).                              sub.2                                               349  H   H   H   CH.sub.3 CH.sub.2 CH.sub.2 CH.sub.2 NHCH.sub.3               350  H   H   H   H                                                                                       ##STR48##                                          351  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH(CH.sub.3)Cl           352  H   H   H   H        (CH.sub.2).sub.11 -Ph                               353  H   H   H   H                                                                                       ##STR49##                                          356  H   H   H   H        CH(CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.2 N(C.sub.2                               H.sub.5).sub.2                                     357  H   H   H   H        (CH.sub.2).sub.9 -Ph                                358  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  OH                                                  361  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 Si(OH).sub.3             362  H   H   H   H        4-hydroxymethylbenzyl                               363  H   H   H   H        CH.sub.2 -cyclopropyl                               364  H   H   H   H        CHCH-Ph                                             365  H   H   H   H                                                                                       ##STR50##                                          367  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 COOH                     368  H   H   H   H        CH.sub.2 CH.sub.2 COOH                              370  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 S(O).sub.2 -Ph           371  H   H   H   H        CH.sub.2 CH.sub.2 S(O).sub.2 CH.sub.3               372  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 O-Ph            373  H   H   H   H                                                                                       ##STR51##                                          374  H   H   H   H                                                                                       ##STR52##                                          375  H   H   H   CH.sub.3 CH.sub.2C CH                                        376  H   H   H   H        CH.sub.2 CH.sub.2 NH.sub.2                          377  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 O-Ph                     378  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 NHCH.sub.2 -Ph           382  H   H   H   H                                                                                       ##STR53##                                          383  H   H   H   H                                                                                       ##STR54##                                          384  H   H   H   H        CH.sub.2 CH.sub.2 S-Ph                              385  H   H   H   H                                                                                       ##STR55##                                          387  H   H   H   H                                                                                       ##STR56##                                          388  H   H   H   H                                                                                       ##STR57##                                          389  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 C(CH.sub.3).sub.2                                  OH                                                  390  H   H   H   H                                                                                       ##STR58##                                          391  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 CH.sub.2 -Ph                                           392  H   H   H   H        CH.sub.2 CH.sub.2 O-Ph                              393  H   H   H   H                                                                                       ##STR59##                                          394  H   H   H   H                                                                                       ##STR60##                                          395  H   H   H   H        CH.sub.2 CH.sub.2 NHC(O)CH.sub.3                    396  H   H   H   H                                                                                       ##STR61##                                          398  H   H   H   H                                                                                       ##STR62##                                          399  H   H   H   H        CH.sub.2 CH.sub.2 C N                               400  H   H   H   CH.sub.3 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -Ph             401  H   H   H   H                                                                                       ##STR63##                                          403  H   H   H   H                                                                                       ##STR64##                                          404  H   H   H   H        CH.sub.2 CH.sub.2 SCH.sub.2 -Ph                     405  H   H   H   H                                                                                       ##STR65##                                          406  H   H   H   H                                                                                       ##STR66##                                          408  H   H   H   H                                                                                       ##STR67##                                          409  H   H   H   H                                                                                       ##STR68##                                          410  H   H   H   H                                                                                       ##STR69##                                          412  H   H   H   H                                                                                       ##STR70##                                          413  H   H   H   H                                                                                       ##STR71##                                          414  H   H   H   H                                                                                       ##STR72##                                          415  H   H   H   H                                                                                       ##STR73##                                          416  H   H   H   H                                                                                       ##STR74##                                          417  H   H   H   H                                                                                       ##STR75##                                          418  H   H   H   H                                                                                       ##STR76##                                          420  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  Cl                                                  421  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 CH(PO.sub.3 H.sub.2).sub.2                             422  H   H   H   H                                                                                       ##STR77##                                          423  H   H   H   H        C(CH.sub.3).sub.2 -Ph                               424  H   H   H   H                                                                                       ##STR78##                                          425  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  CH.sub.2 O-Ph                                       426  H   H   H   H                                                                                       ##STR79##                                          427  H   H   H   H                                                                                       ##STR80##                                          428  H   H   H   H                                                                                       ##STR81##                                          430  H   H   H   H                                                                                       ##STR82##                                          432  H   H   H   H                                                                                       ##STR83##                                          433  H   H   H   H                                                                                       ##STR84##                                          434  H   H   H   H                                                                                       ##STR85##                                          435  H   H   H   H                                                                                       ##STR86##                                          436  H   H   H   H                                                                                       ##STR87##                                          437  H   H   H   H                                                                                       ##STR88##                                          438  H   H   H                                                                nC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 O-Ph                                                   439  H   H   H   H                                                                                       ##STR89##                                          440  H   H   H   CH.sub.2 -Ph                                                                           CH(CH.sub.3)CH.sub.2 CH.sub.2 -Ph                   441  H   H   H   H                                                                                       ##STR90##                                          442  H   H   H   CH.sub.2 CH.sub.2 CH.sub.2 -Ph                                                         CH.sub.2 CH.sub.2 CH.sub.2 -Ph                      443  H   H   H   H                                                                                       ##STR91##                                          444  H   H   H   CH.sub.2 -Ph                                                                           CH.sub.2 CH.sub.2 CH.sub.2 -Ph                      445  H   H   H                                                                nC.sub.4 H.sub.9                                                                   CH.sub.2 CH.sub.2 CH.sub.2 -Ph                                           446  H   H   H   H                                                                                       ##STR92##                                          447  H   H   H   H                                                                                       ##STR93##                                          448  H   H   H   H                                                                                       ##STR94##                                          449  H   H   H   H        CH.sub.2 CH(CH.sub.3)O-Ph                           450  H   H   H   H        CH.sub.2 CH(OH)CH.sub.2 OH                          451  H   H   H   H                                                                                       ##STR95##                                          452  H   H   H   H                                                                                       ##STR96##                                          453  H   H   H   H                                                                                       ##STR97##                                          454  H   H   H   H                                                                                       ##STR98##                                          455  H   H   H                                                                iC.sub.3 H.sub.7                                                                   CH.sub.2 CH.sub.2 CH.sub.2 -Ph                                           456  H   H   H   H                                                                                       ##STR99##                                          457  H   H   H   H                                                                                       ##STR100##                                         458  H   H   H   H        H                                                   459  H   H   H   H        (CH.sub.2).sub.8 OH                                 460  H   H   H                                                                nC.sub.3 H.sub.7                                                                    ##STR101##                                                              461  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  NHCH.sub.2 -Ph                                      462  H   H   H   H                                                                                       ##STR102##                                         463  H   H   H   H                                                                                       ##STR103##                                         465  H   H   H   H                                                                                       ##STR104##                                         466  H   H   H   H                                                                                       ##STR105##                                         467  H   H   H   H        (CH.sub.2).sub.7 O-Ph                               468  H   H   H   H        CH(CH.sub.3)CH.sub.2 O-Ph                           469  H   H   H   H        CH(CH.sub.3)CH.sub.2 -Ph                            470  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 S(O).sub.2                                -Ph                                                 471  H   H   H   H        CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                  S-Ph                                                __________________________________________________________________________     *Hydrochloride salt                                                           **Tributylamine salt                                                          ***Tetrabutylammonium salt                                                    ****Trimethyl sulfonium salt                                             

                                      TABLE II                                    __________________________________________________________________________     ##STR106##                                                                   Comp.                                                                         No. R.sup.1                                                                           R.sup.4                                                                           R.sup.5  R.sup.6   R.sup.7                                        __________________________________________________________________________    140 H   H   H        H         Phenyl Ph!                                     145 H   H   H        H         H                                              152*                                                                              H   H   H        H         C.sub.2 H.sub.5                                153 H   H   H        H                                                        nC.sub.3 H.sub.7                                                              155 H   H   H                                                                 nC.sub.3 H.sub.7                                                              nC.sub.3 H.sub.7                                                              156 H   H   H        H         CH(CH.sub.3).sub.2                             157 H   H   H        H         benzyl                                         158 H   H   H        H                                                        nC.sub.4 H.sub.9                                                              159 H   C.sub.2 H.sub.5                                                                   H        H         benzyl                                         161 H   H   H        H         CH.sub.2 CH(CH.sub.3).sub.2                    162 H   H   H        CH.sub.3  benzyl                                         163 H   H   H        H         cyclopropyl                                    164 H   H   H        C.sub.2 H.sub.5                                                                         C.sub.2 H.sub.5                                165 H   H   H        H         2-methylbenzyl                                 166 H   H   H        H         cyclohexyl                                     167 H   H   H        CH.sub.3                                                 nC.sub.3 H.sub.7                                                              169 OH  H   H        H         H                                              174 OH  H   H        CH.sub.3  benzyl                                         175 OH  H   H        C.sub.2 H.sub.5                                                                         C.sub.2 H.sub.5                                176 OH  H   H        H         CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3           177 OH  H   H        H                                                        iC.sub.3 H.sub.7                                                              178 OH  H   H        CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                    CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3           179 OH  H   H        H                                                        nC.sub.3 H.sub.7                                                              180 OH  H   H        CH.sub.3                                                 nC.sub.5 H.sub.11                                                             181 OH  H   H        H         C.sub.2 H.sub.5                                182 OH  H   H        CH.sub.3  CH.sub.3                                       183 OH  H   H        CH.sub.3                                                 nC.sub.3 H.sub.7                                                              184 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   CH.sub.3                                                              185 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   benzyl                                                                190 OH  H   H        H                                                        iC.sub.3 H.sub.7                                                              191 OH  H   H        CH.sub.3  cyclohexyl                                     192 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   2,4-dichlorobenzyl                                                    193 OH  H   H        H         CH(CH.sub.3)CH.sub.2 CH.sub.3                  194 OH  H   H        CH.sub.3  CH(CH.sub.3)CH.sub.2 CH.sub.3                  195 OH  H   H        C.sub.2 H.sub.5                                          nC.sub.3 H.sub.7                                                              196 OH  H   H                                                                 nC.sub.3 H.sub.7                                                              nC.sub.3 H.sub.7                                                              198 OH  H   H        H                                                                                        ##STR107##                                    199 OH  H   H        H                                                                                        ##STR108##                                    200 OH  H   H        H                                                                                        ##STR109##                                    201 OH  H                                                                     nC.sub.3 H.sub.7                                                                  H   benzyl                                                                202 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   4-methoxybenzyl                                                       203 OH  H                                                                     nC.sub.3 H.sub.7                                                                  H   3-trifluoromethylbenzyl                                               204 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   3-trifluoromethylbenzyl                                               206 OH  H                                                                     nC.sub.3 H.sub.7                                                                  H   3-methoxybenzyl                                                       207 OH  H                                                                     nC.sub.3 H.sub.7                                                                  H                                                                         nC.sub.3 H.sub.7                                                              208 OH  H                                                                     iC.sub.4 H.sub.9                                                                  H   benzyl                                                                209 OH  H   H        H         benzyl                                         210 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   2-chlorobenzyl                                                        211 OH  H   CH.sub.3 H         benzyl                                         212 OH  H   C.sub.2 H.sub.5                                                                        H         benzyl                                         213 OH  H                                                                     iC.sub.3 H.sub.7                                                                  H   4-chlorobenzyl                                                        214 H   H   H        H         CH(CH.sub.3)CH.sub.2 CH.sub.3                  216 H   H   H        H                                                                                        ##STR110##                                    217 H   H   H        H                                                                                        ##STR111##                                    219 H   H   H        H         C.sub.6 H.sub.13                               220 H   H   H        H         CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -Ph        221 H   H   C.sub.2 H.sub.5                                                                        H         H                                              222 H   H   H        H                                                                                        ##STR112##                                    223 H   H   H        H         CH.sub.2 CH.sub.2 CH.sub.2 -Ph                 224 H   H   H        H         CH(CH.sub.3)-Ph                                225 H   H   H        H         4-methylbenzyl                                 226 H   H   H        H         4-chlorobenzyl                                 227 H   H   H        H         CH.sub.3                                       228 H   H   H        H         CH.sub.2 CH.sub.2 CH(CH.sub.3).sub.2           229 H   H   H        H         2-chlorobenzyl                                 230 H   H   H        H         4-phenylbenzyl                                 231 H   H   H        H                                                                                        ##STR113##                                    232 H   H   H        H         CH(CH.sub.3)CH(CH.sub.3).sub.2                 233 H   H   H        H         CH.sub.2 CH(CH.sub.3).sub.2                    234 H   H   H                                                                 nC.sub.3 H.sub.7                                                                  benzyl                                                                    235 H   H   H                                                                 nC.sub.3 H.sub.7                                                                  CH.sub.2 CH(CH.sub.3).sub.2                                               236 H   H   H        C.sub.2 H.sub.5                                          nC.sub.3 H.sub.7                                                              237 H   H   H        H                                                                                        ##STR114##                                    238 H   H   H        H                                                                                        ##STR115##                                    239 H   H   CH.sub.3 H                                                        nC.sub.4 H.sub.9                                                              240 H   H   H        H                                                                                        ##STR116##                                    241 H   H   H        H                                                                                        ##STR117##                                    242 H   H   H        H                                                        nC.sub.5 H.sub.9                                                              243 H   H   H        H                                                                                        ##STR118##                                    244 H   H   C.sub.2 H.sub.5                                                                        H         2-chlorobenzyl                                 247 H   H   C.sub.2 H.sub.5                                                                        H                                                                                        ##STR119##                                    248 H   H   C.sub.2 H.sub.5                                                                        H                                                        nC.sub.4 H.sub.9                                                              257 H   nC.sub.3 H.sub.7                                                                  H        H         benzyl                                         258 H   H                                                                     nC.sub.5 H.sub.11                                                                 H   H                                                                     259 H   H                                                                     iC.sub.3 H.sub.7                                                                  H   H                                                                     260 H   H   H        H         CH.sub.2 CH.sub.2 CH.sub.2 OH                  261 H                                                                         iC.sub.3 H.sub.7                                                                  H   H   benzyl                                                            262 H   H                                                                     nC.sub.3 H.sub.7                                                                  H   H                                                                     263 H   H   benzyl   H         H                                              472 H   CH.sub.3                                                                          H        H         H                                              473 H   CH.sub.3                                                                          CH.sub.3 H         H                                              474 H   H                                                                     nC.sub.3 H.sub.7                                                                  H   H                                                                     475 H   H                                                                     nC.sub.4 H.sub.9                                                                  H   H                                                                     476 H   H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                                     H                                              477 H   H   (CH.sub.2).sub.2 CHCH.sub.2                                                            H         H                                              478 H   H                                                                     iC.sub.4 H.sub.9                                                                  H   H                                                                     479 H   H                                                                     sC.sub.4 H.sub.9                                                                  H   H                                                                     480 H   H   CH.sub.2 CH.sub.2 -Ph                                                                  H         H                                              __________________________________________________________________________     *Diammonium salt                                                         

                  TABLE III                                                       ______________________________________                                         ##STR120##                                                                   Comp.                                                                         No.   n      R.sup.1  R.sup.2                                                                            R.sup.3                                                                            R.sup.4                                                                            R.sup.5                                                                            R.sup.6                                                                            R.sup.7                        ______________________________________                                        249*  3      H        H    H    H    H    H    H                              250*  3      H        H    H    H    H    H    benzyl                         253   2      OH       H    H    H    H    H    CH.sub.3                       254   2      OH       H    H    H    H    H    C.sub.2 H.sub.5                481   3      H        H    H    H    H    H    C.sub.2 H.sub.5                ______________________________________                                         *Triammonium salt                                                        

                                      TABLE IV                                    __________________________________________________________________________     ##STR121##                                                                   Comp. No.                                                                             n R.sup.1                                                                           A                                                               __________________________________________________________________________     3      0 H   NCHNCH                                                           4      0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                              5*     0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                              6      0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                     7      0 OH  CHNCHCH                                                          11**   0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                              13***  0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                              20     0 H                                                                                  ##STR122##                                                      21     0 H                                                                                  ##STR123##                                                      37     0 H                                                                                  ##STR124##                                                      48     0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2            49     0 H                                                                                  ##STR125##                                                      53     0 H                                                                                  ##STR126##                                                      55     0 H                                                                                  ##STR127##                                                      59     0 H   CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2                             65     0 H                                                                                  ##STR128##                                                      71     0 H   CH.sub.2 CHCHCH.sub.2 CH.sub.2                                   73     0 H                                                                                  ##STR129##                                                      84     0 H                                                                                  ##STR130##                                                      87     0 H                                                                                  ##STR131##                                                      91     0 H                                                                                  ##STR132##                                                      92     0 H                                                                                  ##STR133##                                                      94     0 H                                                                                  ##STR134##                                                      96     0 H                                                                                  ##STR135##                                                      97     0 H                                                                                  ##STR136##                                                     100     0 H                                                                                  ##STR137##                                                     101     0 H   CH.sub.2 CH.sub.2 CH.sub.2                                      109     0 H                                                                                  ##STR138##                                                     110     0 H   CHNCHCH                                                         112     0 H                                                                                  ##STR139##                                                     113     0 H                                                                                  ##STR140##                                                     114     0 H                                                                                  ##STR141##                                                     115     0 H                                                                                  ##STR142##                                                     116     0 H                                                                                  ##STR143##                                                     117     0 H                                                                                  ##STR144##                                                     119     0 H                                                                                  ##STR145##                                                     126     0 H                                                                                  ##STR146##                                                     127     0 H                                                                                  ##STR147##                                                     128     0 H                                                                                  ##STR148##                                                     129     0 H                                                                                  ##STR149##                                                     130**** 0 H   CHNCH.sub.2 CH.sub.2 CH.sub.2                                   160     1 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                             168     1 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                    172     1 OH  CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                    173     1 OH                                                                                 ##STR150##                                                     186     1 OH  CHNCHCH                                                         187     1 OH  CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2                            197     1 OH  CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                             215     1 H   CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2                            255     2 OH  CHNCHCH                                                         264     0 H   CH.sub.2 CH(OH)CH.sub.2 CH.sub.2 CH.sub.2                       265     0 H   CH.sub.2 CHCHCH.sub.2                                           266     0 H                                                                                  ##STR151##                                                     268     0 H                                                                                  ##STR152##                                                     275     0 H                                                                                  ##STR153##                                                     278     0 H                                                                                  ##STR154##                                                     283     0 H                                                                                  ##STR155##                                                     285     0 H                                                                                  ##STR156##                                                     288     0 H                                                                                  ##STR157##                                                     291     0 H                                                                                  ##STR158##                                                     293     0 H                                                                                  ##STR159##                                                     300     0 H                                                                                  ##STR160##                                                             0 H                                                                                  ##STR161##                                                     301                                                                                   0 H                                                                                  ##STR162##                                                     302     0 H                                                                                  ##STR163##                                                     305     0 H                                                                                  ##STR164##                                                     306     0 H                                                                                  ##STR165##                                                     307     0 H                                                                                  ##STR166##                                                     310     0 H                                                                                  ##STR167##                                                     316     0 H                                                                                  ##STR168##                                                     321     0 H                                                                                  ##STR169##                                                     322     0 H                                                                                  ##STR170##                                                     325     0 H                                                                                  ##STR171##                                                     328     0 H                                                                                  ##STR172##                                                     339     0 H                                                                                  ##STR173##                                                     340     0 H                                                                                  ##STR174##                                                     342     0 H                                                                                  ##STR175##                                                     354     0 H   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                         CH.sub.2 CH.sub.2                                               355     0 H                                                                                  ##STR176##                                                     359     0 H                                                                                  ##STR177##                                                     360                                                                                    ##STR178##                                                                      ##STR179##                                                                        ##STR180##                                                     366     0 H                                                                                  ##STR181##                                                     369                                                                                    ##STR182##                                                                      ##STR183##                                                                        ##STR184##                                                     379     0 H                                                                                  ##STR185##                                                     380     0 H                                                                                  ##STR186##                                                     381     0 H                                                                                  ##STR187##                                                     386     0 H                                                                                  ##STR188##                                                     397     0 H                                                                                  ##STR189##                                                     402     0 H                                                                                  ##STR190##                                                     407     0 H                                                                                  ##STR191##                                                     411     0 H                                                                                  ##STR192##                                                     419     0 H                                                                                  ##STR193##                                                     429     0 H                                                                                  ##STR194##                                                     431     0 H                                                                                  ##STR195##                                                     464     0 H                                                                                  ##STR196##                                                     481     1 NH.sub.2                                                                          CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                    __________________________________________________________________________     *Tetramethylammonium salt                                                     **Tributylamine salt                                                          ***Trimethylsulfonium salt                                                    ****Diammonium salt                                                      

                  TABLE V                                                         ______________________________________                                         ##STR197##                                                                   Comp. No.                                                                             n     R.sup.1 R.sup.2                                                                           R.sup.3                                                                             X                                             ______________________________________                                         9      0     OH                                                                                               ##STR198##                                    10*    0     OH                                                                                               ##STR199##                                    17     0     H                                                                                                ##STR200##                                    19     0     OH                                                                                               ##STR201##                                   139     1     H       H   H                                                                                    ##STR202##                                   141     1     H       H   H                                                                                    ##STR203##                                   142**   1     H       H   H                                                                                    ##STR204##                                   143     1     H       H   H                                                                                    ##STR205##                                   144***  1     H       H   H                                                                                    ##STR206##                                   146*    1     H       H   H                                                                                    ##STR207##                                   147     1     H       H   H                                                                                    ##STR208##                                   148     1     H       H   H                                                                                    ##STR209##                                   149     1     H       H   H                                                                                    ##STR210##                                   150**   1     H       H   H                                                                                    ##STR211##                                   151**   1     H       H   H                                                                                    ##STR212##                                   154     1     H       H   H                                                                                    ##STR213##                                   170     1     OH      H   H                                                                                    ##STR214##                                   171     1     OH      H   H                                                                                    ##STR215##                                   188     1     OH      H   H                                                                                    ##STR216##                                   189     1     OH      H   H                                                                                    ##STR217##                                   205     1     OH      H   H                                                                                    ##STR218##                                   218     1     H       H   CH.sub.3                                                                             ##STR219##                                   245**** 1     H       H   H                                                                                    ##STR220##                                   251     1     H       H   H                                                                                    ##STR221##                                   252     1     H       H   H                                                                                    ##STR222##                                   256     1     OH      H   H                                                                                    ##STR223##                                   ______________________________________                                         *Tributylammonium salt                                                        **Tetramethylammonium salt                                                    ***Sodium salt                                                                ****Triammonium salt                                                     

HERBICIDAL SCREENING TESTS

The compounds listed in the foregoing tables were tested for herbicidalactivity by various methods and at various rates of application. Theresults of some of these tests are given below. Results obtained inherbicidal screening are affected by a number of factors including: theamount of sunlight, soil type, soil pH, temperature, humidity, depth ofplanting, plant growth stage, application rate as well as many otherfactors. All testing procedures are administered with the least amountof variability possible. State of the art equipment and techniques areemployed to enable the screening process to remain consistent andreliable.

PRE-EMERGENCE HERBICIDAL SCREENING TEST

On the day preceding treatment, seeds of several different weed specieswere planted in sandy loam soil containing only trace organic matter.Propagules were sown in individual rows using one species per row acrossthe width of an aluminum flat (19.5×9.5×6 cm). The grass weeds plantedwere green foxtail (Setaria viridis) ("SETVI"), wild oat (Avena fatua)("AVEFA"), barnyardgrass (Echinochloa crusgalli) ("ECHCG"). Broadleafweeds utilized were wild mustard (Sinapis arvensis) ("SINAR"),velvetleaf (Abutilon theophrasti) ("ABUTH") and morningglory (Ipomoeaspp.) ("IPOSS"). Additionally, yellow nutsedge (Cyperus esculentus)("CYPES"), nutlets were sown. Seeding depths ranged from 1.0 to 1.5 cmand plant densities ranged from 3 to 25 plants per row depending onindividual plant species.

Solutions of the test compounds were prepared by weighing out 18.8 and74.7 mg for 1.0 and 4.0 kilograms (acid equivalent) per hectare (kg/ha)applications, respectively, of the test compound into a 60 ml wide-mouthbottle, then dissolving the compound in 14.0 ml of deionized watercontaining 0.5% v/v Tween 20®(polyoxyethylene sorbitan monolaurateemulsifier) as a surfactant. Additional solvents, not exceeding 2 ml(15% of spray volume), were used if needed to dissolve the compound.

The soil surface was sprayed inside an enclosed linear spray table withthe nozzle set at 30.5 cm (12 inches) above the soil line. The spraytable was calibrated to deliver 748 L/ha (80 gal/A) with the applicationrate being 4.0 kg/ha or 1.0 kg/ha. After treatment, the flats wereplaced into a greenhouse and watered as needed. The greenhouseenvironmental systems provided the plants with natural and artificial(via metal halide lamps) lighting to attain 14 hours of light per day.Day and night temperatures were maintained at 29° and 21° C.,respectively.

The degree of weed control was evaluated and recorded 17-21 days aftertreatment as a percentage of weed control as compared to the growth ofthe same species of the same age in an untreated control flat. Percentcontrol is the total injury to the plants due to all factors including:inhibited emergence, stunting, malformation, chlorosis and other typesof plant injury. The control ratings range from 0 to 100 percent, where0% represents no effect with growth equal to the untreated control andwhere 100% represents complete kill. A dash (-) indicates that no testwas performed at that level of application.

POST-EMERGENCE HERBICIDAL EVALUATION

The soil was prepared and seeded with the same species and methodologydescribed for the pre-emergence test. Post-emergence flats were placedin the greenhouse under the same environmental conditions as describedfor the pre-emergence flats and watered as needed. Plants were grown for10 to 12 days (or to the appropriate growth stage) prior to compoundapplication. Grasses were sprayed at a 3 to 4 leaf stage and broadleavesat a 1 to 2 leaf stage. Yellow nutsedge was 5 to 7 cm tall atapplication.

Plants were sprayed 30.5 cm (12 inches) above the foliage with the samespray solution as prepared for the pre-emergence test. The applicationrate was 4.0 kg/ha or 1.0 kg/ha. Treated plants were then returned to agreenhouse and watered daily without wetting the foliage. The degree ofweed control was evaluated 17-21 days after application and recorded aspercentage of control as compared to the growth of the same species inan untreated control flat of the same age. The percent control scale(0-100%) used to evaluate the pre-emergence treatment was also appliedto the post-emergence treatment, with a dash (-) again indicating thatno test was performed at that level of application.

                                      TABLE VI                                    __________________________________________________________________________    Post-Emergence Testing                                                        Comp.                                                                             Rate                                                                      No. kg/ha                                                                            AVEFA                                                                             ECHCG                                                                             SETVI                                                                             ABUTH                                                                              IPOSS                                                                             SINAR                                                                             CYPES                                         __________________________________________________________________________    1   4.0                                                                              0   0   0   0    --  0   0                                             2   4.0                                                                              5   95  95  25   60  90  20                                            3   4.0                                                                              10  5   30  0    5   60  0                                             4   4.0                                                                              100 100 100 100  100 100 50                                            5   4.0                                                                              100 100 100 100  100 100 80                                            6   4.0                                                                              100 100 100 70   100 100 20                                            7   4.0                                                                              60  100 100 75   70  100 10                                            8   4.0                                                                              0   0   0   0    0   0   0                                             9   4.0                                                                              0   0   60  0    0   90  5                                             10  4.0                                                                              10  10  70  5    10  80  15                                            11  1.0                                                                              100 95  95  80   70  100 25                                            12  1.0                                                                              100 100 100 70   95  100 30                                            13  1.0                                                                              60  90  100 20   20  100 5                                             14  4.0                                                                              98  98  98  60   60  100 10                                            15  4.0                                                                              50  60  60  15   70  100 25                                            16  4.0                                                                              85  50  60  5    60  100 15                                            17  4.0                                                                              0   0   10  0    0   10  0                                             18  4.0                                                                              5   5   50  0    5   85  0                                             19  4.0                                                                              60  30  100 30   30  100 15                                            20  4.0                                                                              100 85  85  50   90  100 5                                             21  4.0                                                                              30  50  50  0    30  95  0                                             22  4.0                                                                              100 98  98  98   90  100 70                                            23  1.0                                                                              40  40  80  15   10  95  5                                             24  1.0                                                                              100 100 100 70   100 100 25                                            25  1.0                                                                              100 100 100 60   100 100 20                                            27  1.0                                                                              70  90  95  20   10  85  15                                            28  1.0                                                                              0   0   0   0    0   0   0                                             29  1.0                                                                              80  100 90  10   10  100 20                                            30  1.0                                                                              75  50  60  0    10  50  0                                             31  1.0                                                                              90  70  80  20   10  10  30                                            32  1.0                                                                              100 98  98  30   70  100 50                                            33  1.0                                                                              100 100 98  100  60  100 10                                            34  1.0                                                                              5   10  40  0    0   50  0                                             35  1.0                                                                              5   0   60  10   0   10  0                                             36  1.0                                                                              40  60  50  0    0   10  15                                            37  1.0                                                                              50  30  50  0    10  30  5                                             38  1.0                                                                              0   15  20  5    5   40  0                                             39  4.0                                                                              0   0   0   0    0   0   0                                             40  1.0                                                                              98  98  85  0    5   30  10                                            41  1.0                                                                              95  60  95  0    0   98  25                                            42  1.0                                                                              100 100 100 98   90  100 85                                            43  1.0                                                                              80  80  60  20   10  40  5                                             44  1.0                                                                              80  90  90  75   5   100 75                                            45  1.0                                                                              80  85  50  15   5   60  5                                             46  1.0                                                                              80  50  40  5    10  15  15                                            47  1.0                                                                              60  5   30  5    5   50  10                                            48  1.0                                                                              60  60  60  0    15  85  0                                             49  1.0                                                                              90  90  95  5    30  100 5                                             50  1.0                                                                              0   0   0   0    0   0   0                                             51  1.0                                                                              100 95  100 75   85  100 25                                            52  1.0                                                                              100 100 95  50   65  100 10                                            53  1.0                                                                              5   0   5   0    5   25  0                                             54  1.0                                                                              95  95  95  60   60  100 15                                            55  1.0                                                                              98  15  50  0    30  25  0                                             56  1.0                                                                              0   0   0   0    0   0   0                                             57  1.0                                                                              95  95  100 10   15  98  10                                            58  1.0                                                                              40  70  90  25   5   20  5                                             59  1.0                                                                              95  25  40  5    95  15  0                                             60  1.0                                                                              100 100 100 70   90  100 10                                            61  1.0                                                                              20  0   5   0    0   0   0                                             62  1.0                                                                              85  90  80  10   10  95  10                                            63  1.0                                                                              100 95  95  85   85  100 60                                            64  1.0                                                                              100 95  95  10   90  100 20                                            65  1.0                                                                              100 98  98  30   60  100 5                                             66  1.0                                                                              95  60  75  5    10  20  20                                            67  1.0                                                                              95  70  30  10   10  10  10                                            68  1.0                                                                              30  20  30  0    5   20  15                                            69  1.0                                                                              10  30  20  0    10  10  10                                            70  1.0                                                                              90  100 100 60   10  90  60                                            71  1.0                                                                              100 100 100 90   100 100 50                                            72  1.0                                                                              50  15  20  5    0   5   10                                            73  1.0                                                                              0   0   10  0    0   5   0                                             74  1.0                                                                              100 98  95  60   95  100 50                                            75  1.0                                                                              60  50  15  5    10  10  10                                            76  1.0                                                                              50  15  10  5    5   15  5                                             77  1.0                                                                              60  10  5   0    5   5   5                                             78  1.0                                                                              75  30  15  10   iO  5   5                                             79  1.0                                                                              90  70  25  5    15  25  10                                            80  1.0                                                                              50  60  85  5    5   85  5                                             81  1.0                                                                              98  100 98  10   15  100 30                                            82  1.0                                                                              100 100 98  50   35  100 30                                            83  1.0                                                                              100 98  98  15   25  100 50                                            84  1.0                                                                              15  40  20  0    10  90  0                                             85  1.0                                                                              100 98  98  70   15  100 5                                             86  1.0                                                                              100 100 100 75   20  100 20                                            87  1.0                                                                              98  100 98  70   30  90  5                                             88  1.0                                                                              0   0   10  0    5   10  0                                             89  1.0                                                                              75  80  100 60   10  100 30                                            90  1.0                                                                              100 100 100 95   98  100 60                                            91  1.0                                                                              100 100 100 80   90  100 15                                            92  1.0                                                                              100 98  100 98   90  100 10                                            93  1.0                                                                              0   10  10  10   5   10  0                                             94  1.0                                                                              40  40  80  10   15  15  10                                            95  1.0                                                                              85  90  95  30   20  90  5                                             96  1.0                                                                              10  30  30  10   5   20  0                                             97  1.0                                                                              100 98  95  50   50  98  5                                             98  1.0                                                                              100 98  95  70   100 100 15                                            99  1.0                                                                              100 100 90  70   30  90  10                                            100 1.0                                                                              100 60  70  40   20  30  0                                             101 1.0                                                                              50  90  70  10   25  100 5                                             102 1.0                                                                              100 85  95  15   30  85  10                                            103 1.0                                                                              0   5   10  20   5   10  0                                             104 1.0                                                                              75  70  60  10   5   20  5                                             105 1.0                                                                              50  60  15  5    5   15  10                                            106 1.0                                                                              50  50  50  0    5   15  10                                            107 1.0                                                                              60  30  30  5    10  30  10                                            108 1.0                                                                              30  50  20  5    5   15  0                                             109 1.0                                                                              85  90  98  30   15  100 5                                             110 1.0                                                                              100 98  100 75   100 100 30                                            111 1.0                                                                              10  15  10  5    10  20  0                                             112 1.0                                                                              0   5   10  0    5   10  0                                             113 1.0                                                                              0   10  5   0    5   5   0                                             114 1.0                                                                              100 98  98  70   20  98  5                                             115 1.0                                                                              100 70  40  5    10  20  0                                             130 1.0                                                                              95  100 100 100  100 100 5                                             139 4.0                                                                              0   0   0   0    --  0   0                                             140 4.0                                                                              0   5   20  0    --  10  0                                             141 1.0                                                                              90  100 100 100  100 100 20                                            142 4.0                                                                              100 100 100 100  100 100 30                                            143 4.0                                                                              20  5   25  0    15  100 0                                             144 4.0                                                                              100 100 100 100  100 100 50                                            145 4.0                                                                              5   10  95  60   90  100 70                                            146 1.0                                                                              90  100 100 100  100 100 25                                            147 1.0                                                                              100 100 98  60   40  100 15                                            148 1.0                                                                              98  100 95  85   60  100 10                                            149 1.0                                                                              10  5   10  10   0   30  0                                             150 4.0                                                                              70  99  90  75   80  --  20                                            151 4.0                                                                              78  97  98  80   85  --  25                                            152 1.0                                                                              100 95  98  75   40  100 25                                            153 1.0                                                                              90  95  98  50   70  98  20                                            154 1.0                                                                              80  95  95  70   15  90  15                                            155 1.0                                                                              95  95  98  60   15  80  10                                            156 1.0                                                                              10  50  95  0    20  20  10                                            157 1.0                                                                              100 98  100 95   20  40  60                                            158 1.0                                                                              60  60  75  100  10  20  10                                            159 1.0                                                                              98  98  100 100  15  70  15                                            160 1.0                                                                              100 98  95  100  70  100 15                                            161 1.0                                                                              80  90  98  100  75  100 50                                            162 1.0                                                                              60  70  70  30   10  30  10                                            163 1.0                                                                              80  75  95  70   20  60  30                                            164 1.0                                                                              70  90  90  20   20  100 10                                            165 1.0                                                                              85  90  98  40   20  30  40                                            166 1.0                                                                              70  80  90  10   25  100 50                                            167 1.0                                                                              100 95  98  95   85  100 40                                            168 1.0                                                                              80  85  90  25   15  95  5                                             169 4.0                                                                              10  60  60  10   0   25  5                                             170 4.0                                                                              15  20  90  30   30  100 5                                             171 4.0                                                                              100 100 100 100  75  100 15                                            172 4.0                                                                              5   20  60  0    30  90  0                                             173 4.0                                                                              0   0   0   0    0   0   0                                             174 4.0                                                                              20  50  40  25   0   15  15                                            175 4.0                                                                              15  15  90  40   20  100 0                                             176 4.0                                                                              0   5   5   0    0   15  0                                             177 4.0                                                                              0   0   15  0    5   15  0                                             178 4.0                                                                              5   0   10  0    5   15  0                                             179 4.0                                                                              85  85  90  25   20  90  10                                            180 4.0                                                                              30  50  98  25   5   100 0                                             181 4.0                                                                              25  50  85  30   30  100 15                                            182 4.0                                                                              0   5   90  10   5   30  5                                             183 4.0                                                                              90  98  98  85   80  100 10                                            184 4.0                                                                              90  95  100 100  60  100 20                                            185 4.0                                                                              90  100 85  20   20  100 5                                             186 4.0                                                                              0   5   20  0    0   20  0                                             187 4.0                                                                              0   0   10  0    0   0   0                                             188 4.0                                                                              5   20  90  80   10  95  5                                             189 4.0                                                                              80  100 95  100  75  100 25                                            190 4.0                                                                              0   20  40  0    5   50  0                                             191 4.0                                                                              0   20  10  15   5   15  0                                             192 4.0                                                                              5   0   5   5    10  85  5                                             193 4.0                                                                              5   30  20  0    5   15  0                                             194 4.0                                                                              70  95  90  80   85  100 60                                            195 4.0                                                                              75  90  95  95   50  100 15                                            196 4.0                                                                              60  95  98  95   50  100 5                                             197 4.0                                                                              30  70  95  70   15  100 15                                            198 4.0                                                                              50  98  90  85   70  100 80                                            199 4.0                                                                              20  98  95  90   20  100 80                                            200 4.0                                                                              10  10  30  60   30  80  50                                            201 4.0                                                                              98  98  20  50   50  100 5                                             202 4.0                                                                              10  10  50  0    5   100 10                                            203 4.0                                                                              5   5   10  10   10  70  10                                            204 4.0                                                                              5   5   5   10   5   50  10                                            205 4.0                                                                              0   0   0   0    0   10  0                                             206 4.0                                                                              40  98  30  10   20  80  10                                            207 4.0                                                                              80  90  90  70   30  100 5                                             208 4.0                                                                              0   10  5   5    0   40  0                                             209 4.0                                                                              40  40  30  15   20  80  40                                            210 4.0                                                                              95  75  15  100  15  100 10                                            211 1.0                                                                              20  10  5   5    5   15  0                                             212 1.0                                                                              80  95  75  85   5   95  10                                            213 1.0                                                                              15  15  25  15   10  40  5                                             214 1.0                                                                              60  80  95  5    30  80  25                                            215 1.0                                                                              5   15  60  20   0   30  0                                             216 1.0                                                                              90  100 98  95   90  100 85                                            217 1.0                                                                              70  85  85  5    5   50  20                                            218 1.0                                                                              40  15  30  0    5   10  0                                             219 1.0                                                                              90  85  60  10   5   85  35                                            220 1.0                                                                              95  95  95  40   10  100 50                                            221 1.0                                                                              95  100 95  65   40  100 40                                            222 1.0                                                                              60  95  90  65   65  100 35                                            223 1.0                                                                              75  95  95  25   15  100 35                                            224 1.0                                                                              98  98  100 85   35  100 75                                            225 1.0                                                                              90  98  98  65   50  100 65                                            226 1.0                                                                              85  90  95  25   15  70  30                                            227 1.0                                                                              75  95  95  10   10  95  15                                            228 1.0                                                                              100 98  98  90   10  85  50                                            229 1.0                                                                              98  95  98  60   5   40  30                                            230 1.0                                                                              10  15  50  0    5   60  0                                             231 1.0                                                                              98  95  98  65   65  100 40                                            232 1.0                                                                              85  94  98  60   75  100 30                                            233 1.0                                                                              95  90  98  100  90  100 25                                            234 1.0                                                                              75  60  70  35   20  25  20                                            235 1.0                                                                              70  60  95  70   20  80  15                                            236 1.0                                                                              90  90  98  70   75  100 20                                            237 1.0                                                                              98  98  100 75   15  100 70                                            238 1.0                                                                              70  40  60  25   10  70  20                                            239 1.0                                                                              100 100 98  80   15  100 20                                            240 1.0                                                                              40  70  85  20   5   60  15                                            241 1.0                                                                              90  95  98  70   20  90  10                                            242 1.0                                                                              98  75  95  65   15  20  10                                            243 1.0                                                                              75  40  70  60   10  90  10                                            244 1.0                                                                              98  98  80  60   20  40  20                                            245 1.0                                                                              100 100 100 95   85  100 25                                            247 1.0                                                                              100 100 100 60   15  90  65                                            248 1.0                                                                              100 98  98  75   40  100 20                                            249 4.0                                                                              85  60  98  15   25  100 35                                            250 4.0                                                                              90  35  60  15   5   95  20                                            251 4.0                                                                              0   0   0   0    0   0   0                                             252 4.0                                                                              0   10  70  15   30  100 5                                             253 4.0                                                                              0   0   0   60   15  10  0                                             254 4.0                                                                              0   0   10  5    0   15  0                                             255 4.0                                                                              0   0   10  0    0   0   0                                             256 4.0                                                                              0   0   0   0    0   0   0                                             257 1.0                                                                              100 100 100 90   65  100 60                                            258 1.0                                                                              100 100 100 98   30  100 95                                            259 1.0                                                                              100 100 100 100  65  100 65                                            260 1.0                                                                              75  65  98  0    20  95  15                                            261 1.0                                                                              100 100 100 80   75  100 50                                            262 1.0                                                                              100 98  100 65   60  100 60                                            264 1.0                                                                              100 95  100 60   95  100 10                                            265 1.0                                                                              100 95  100 60   50  100 40                                            266 1.0                                                                              30  15  10  0    15  15  5                                             267 1.0                                                                              100 100 100 98   70  100 70                                            268 1.0                                                                              30  10  5   0    5   15  0                                             269 1.0                                                                              40  10  10  100  10  25  0                                             270 1.0                                                                              100 100 100 100  85  100 80                                            271 1.0                                                                              80  90  30  50   15  15  20                                            272 1.0                                                                              20  5   10  0    0   10  0                                             273 1.0                                                                              98  100 98  40   20  85  90                                            274 1.0                                                                              100 100 100 60   30  100 60                                            275 1.0                                                                              90  70  60  75   30  30  5                                             276 4.0                                                                              60  60  60  60   10  25  10                                            277 1.0                                                                              100 90  90  15   30  100 10                                            278 1.0                                                                              85  50  30  30   15  30  5                                             279 1.0                                                                              100 100 95  60   80  100 60                                            280 1.0                                                                              100 80  75  50   30  25  10                                            281 1.0                                                                              60  20  10  0    10  15  30                                            282 1.0                                                                              10  20  15  0    5   40  10                                            283 1.0                                                                              100 85  95  85   30  100 50                                            284 1.0                                                                              80  90  95  20   20  75  30                                            285 1.0                                                                              15  40  60  0    10  60  40                                            286 1.0                                                                              70  80  98  5    10  20  10                                            287 1.0                                                                              40  75  30  5    10  15  15                                            288 1.0                                                                              0   5   5   50   0   15  0                                             289 1.0                                                                              75  75  40  40   15  40  15                                            290 1.0                                                                              0   0   5   0    0   10  0                                             291 1.0                                                                              40  10  20  5    10  15  5                                             292 1.0                                                                              0   0   5   15   30  20  0                                             293 4.0                                                                              0   0   0   5    10  10  0                                             294 1.0                                                                              75  75  98  5    10  60  10                                            295 1.0                                                                              100 98  100 85   30  100 5                                             296 1.0                                                                              20  90  40  0    5   30  40                                            297 1.0                                                                              30  30  60  5    10  30  10                                            298 1.0                                                                              0   10  20  0    5   15  10                                            299 1.0                                                                              0   0   0   0    0   0   0                                             300 1.0                                                                              70  90  95  50   40  100 10                                            301 1.0                                                                              70  25  50  25   10  70  5                                             302 1.0                                                                              100 15  50  10   10  85  20                                            303 1.0                                                                              100 100 100 50   50  100 60                                            304 1.0                                                                              98  98  98  5    40  95  30                                            305 1.0                                                                              5   10  10  10   10  10  0                                             306 1.0                                                                              70  30  30  5    10  15  10                                            307 1.0                                                                              60  40  50  10   5   60  15                                            308 1.0                                                                              95  95  90  70   15  100 15                                            309 1.0                                                                              20  25  70  0    10  30  5                                             310 1.0                                                                              60  70  50  5    15  15  5                                             311 1.0                                                                              70  95  95  30   30  60  25                                            312 1.0                                                                              25  10  10  0    5   20  0                                             313 1.0                                                                              100 90  90  75   80  100 60                                            314 1.0                                                                              65  70  95  0    5   15  5                                             315 1.0                                                                              0   10  50  0    0   5   0                                             316 1.0                                                                              70  50  85  15   5   90  5                                             317 1.0                                                                              20  60  80  0    5   60  0                                             318 1.0                                                                              100 100 100 75   70  100 75                                            319 1.0                                                                              75  95  95  10   15  75  5                                             320 1.0                                                                              65  90  95  0    10  70  15                                            321 1.0                                                                              75  20  25  5    15  20  20                                            322 1.0.                                                                             100 98  100 40   30  100 40                                            323 1.0                                                                              95  95  95  5    10  75  10                                            324 1.0                                                                              75  80  90  40   5   40  40                                            325 1.0                                                                              90  100 100 10   15  98  30                                            326 1.0                                                                              75  95  95  0    15  100 20                                            327 1.0                                                                              90  95  98  15   10  65  15                                            328 1.0                                                                              95  80  95  10   25  100 15                                            329 1.0                                                                              85  40  75  5    10  60  30                                            330 1.0                                                                              100 98  100 90   90  100 40                                            331 1.0                                                                              90  95  90  75   55  80  25                                            332 1.0                                                                              20  0   5   5    0   5   0                                             333 1.0                                                                              80  70  100 50   25  60  30                                            334 1.0                                                                              98  95  100 50   30  100 40                                            335 1.0                                                                              100 95  100 50   10  100 30                                            336 1.0                                                                              50  70  85  20   5   100 15                                            337 1.0                                                                              85  95  80  15   20  50  5                                             338 1.0                                                                              0   0   5   15   5   70  0                                             339 1.0                                                                              15  20  70  0    5   30  10                                            340 1.0                                                                              20  40  50  5    0   20  0                                             341 1.0                                                                              90  98  95  70   5   100 40                                            342 1.0                                                                              10  10  15  5    5   25  0                                             343 1.0                                                                              0   0   0   0    5   10  0                                             344 1.0                                                                              100 100 100 5    10  100 40                                            345 1.0                                                                              0   10  10  0    0   15  5                                             346 1.0                                                                              90  100 100 10   5   100 40                                            347 1.0                                                                              100 100 90  40   25  60  40                                            348 1.0                                                                              0   0   5   0    0   10  0                                             349 1.0                                                                              0   0   0   0    10  20  0                                             350 1.0                                                                              100 98  98  30   25  100 10                                            351 1.0                                                                              30  25  20  5    10  25  5                                             352 1.0                                                                              0   0   5   0    5   10  0                                             353 1.0                                                                              0   0   0   0    0   0   0                                             354 1.0                                                                              40  10  10  5    5   15  10                                            355 1.0                                                                              100 100 100 40   40  100 30                                            356 1.0                                                                              0   0   10  0    5   20  0                                             357 1.0                                                                              0   0   10  0    5   5   0                                             358 1.0                                                                              70  95  90  0    5   80  15                                            359 1.0                                                                              10  10  30  0    5   20  0                                             360 1.0                                                                              75  70  90  0    10  40  0                                             361 1.0                                                                              0   0   0   0    20  5   0                                             362 1.0                                                                              0   0   0   0    0   0   0                                             363 1.0                                                                              100 98  100 5    10  100 25                                            364 1.0                                                                              0   0   0   0    5   0   0                                             365 1.0                                                                              0   0   0   0    0   10  0                                             366 1.0                                                                              100 95  100 20   20  100 10                                            367 1.0                                                                              0   0   0   0    0   0   0                                             368 1.0                                                                              0   0   0   0    5   5   0                                             369 1.0                                                                              0   0   0   0    0   10  0                                             370 1.0                                                                              15  50  60  0    5   25  5                                             371 1.0                                                                              10  15  10  0    5   5   0                                             372 1.0                                                                              100 100 100 20   10  100 80                                            373 1.0                                                                              85  95  100 5    5   100 30                                            374 1.0                                                                              0   10  20  0    10  60  0                                             375 1.0                                                                              100 95  95  0    20  98  25                                            376 1.0                                                                              0   0   0   0    0   0   0                                             377 1.0                                                                              100 100 100 10   10  98  50                                            378 1.0                                                                              0   0   0   0    0   0   0                                             379 1.0                                                                              100 85  98  0    15  40  10                                            380 1.0                                                                              0   0   0   0    0   0   0                                             381 1.0                                                                              0   0   0   0    0   0   0                                             382 1.0                                                                              100 95  98  10   20  95  35                                            383 1.0                                                                              100 100 100 70   10  100 90                                            384 1.0                                                                              100 50  90  0    5   65  5                                             385 1.0                                                                              65  25  30  0    5   60  10                                            386 1.0                                                                              10  10  15  0    10  10  0                                             387 1.0                                                                              30  5   10  0    5   10  0                                             388 1.0                                                                              80  50  80  10   5   60  60                                            389 1.0                                                                              0   0   5   0    0   0   0                                             390 4.0                                                                              0   0   0   0    0   5   0                                             391 1.0                                                                              95  98  85  25   30  80  15                                            392 1.0                                                                              95  70  98  10   10  95  40                                            393 1.0                                                                              85  75  95  10   60  100 5                                             394 1.0                                                                              90  75  95  30   5   100 30                                            395 1.0                                                                              0   5   15  0    5   15  0                                             396 1.0                                                                              85  50  85  0    0   80  10                                            397 1.0                                                                              90  50  70  10   5   5   5                                             398 1.0                                                                              30  15  70  0    10  20  10                                            399 1.0                                                                              0   10  85  0    5   30  0                                             400 1.0                                                                              100 100 100 0    20  100 20                                            401 1.0                                                                              100 70  100 5    10  85  5                                             492 1.0                                                                              0   0   0   0    0   0   0                                             403 1.0                                                                              95  20  50  5    10  35  10                                            404 1.0                                                                              85  10  90  0    10  15  0                                             405 1.0                                                                              80  40  95  0    15  10  5                                             406 1.0                                                                              20  75  95  75   10  70  60                                            407 1.0                                                                              10  5   15  60   10  10  0                                             408 1.0                                                                              100 95  100 40   10  100 15                                            409 1.0                                                                              0   0   0   10   0   10  0                                             410 1.0                                                                              75  80  95  35   20  100 65                                            411 1.0                                                                              0   20  60  0    5   40  0                                             412 1.0                                                                              20  60  95  35   5   100 50                                            413 1.0                                                                              60  25  70  0    5   65  5                                             414 1.0                                                                              25  10  70  20   5   75  0                                             415 4.0                                                                              0   10  0   0    5   0   0                                             416 1.0                                                                              75  70  60  5    10  10  10                                            417 1.0                                                                              95  98  60  10   15  60  50                                            418 1.0                                                                              95  25  95  0    15  75  10                                            419 1.0                                                                              100 100 100 10   10  90  15                                            420 1.0                                                                              90  90  95  5    5   100 20                                            421 1.0                                                                              15  20  95  10   5   60  5                                             422 1.0                                                                              10  0   0   0    0   0   0                                             423 1.0                                                                              80  60  60  0    5   10  5                                             424 4.0                                                                              0   0   0   0    10  0   0                                             425 1.0                                                                              100 98  100 10   10  100 50                                            426 1.0                                                                              50  30  90  0    25  25  0                                             427 1.0                                                                              15  20  25  0    5   5   0                                             423 1.0                                                                              20  25  85  5    5   75  0                                             429 1.0                                                                              0   0   0   0    0   0   0                                             430 1.0                                                                              0   0   0   0    5   10  0                                             431 1.0                                                                              100 98  100 30   15  100 20                                            432 1.0                                                                              25  10  15  0    10  15  10                                            433 1.0                                                                              100 100 100 20   40  100 60                                            434 1.0                                                                              100 100 100 40   20  100 50                                            435 1.0                                                                              75  65  70  0    5   10  5                                             436 1.0                                                                              50  50  50  15   5   20  10                                            437 1.0                                                                              80  98  98  0    20  100 75                                            438 1.0                                                                              98  100 60  10   10  60  20                                            439 1.0                                                                              85  95  95  0    5   100 20                                            440 1.0                                                                              5   10  15  0    0   5   0                                             441 1.0                                                                              0   0   0   0    0   0   0                                             442 1.0                                                                              10  10  10  0    0   5   0                                             443 1.0                                                                              0   0   5   0    0   5   0                                             444 1.0                                                                              10  10  10  10   5   15  10                                            445 1.0                                                                              98  98  85  5    10  25  25                                            446 1.0                                                                              10  0   0   0    0   0   0                                             447 1.0                                                                              80  95  90  225  10  70  30                                            448 1.0                                                                              85  80  70  40   5   70  5                                             449 1.0                                                                              70  80  90  10   5   50  10                                            450 1.0                                                                              25  75  85  5    5   60  0                                             451 1.0                                                                              0   0   0   0    0   10  0                                             452 1.0                                                                              0   0   0   0    0   0   0                                             453 1.0                                                                              10  10  10  0    5   5   0                                             454 1.0                                                                              5   15  40  0    5   15  0                                             455 1.0                                                                              85  95  65  0    20  60  40                                            456 1.0                                                                              0   0   15  0    5   20  0                                             457 1.0                                                                              85  85  85  10   5   60  15                                            458 1.0                                                                              90  95  98  50   20  95  60                                            459 1.0                                                                              60  60  95  0    0   90  5                                             460 1.0                                                                              75  70  60  10   10  40  20                                            461 1.0                                                                              10  5   5   0    0   10  0                                             462 1.0                                                                              70  80  95  0    5   50  0                                             463 1.0                                                                              10  0   10  0    5   10  0                                             464 1.0                                                                              20  0   10  0    5   25  0                                             465 1.0                                                                              60  25  40  0    5   5   5                                             466 1.0                                                                              30  5   5   0    0   10  5                                             467 1.0                                                                              100 80  90  5    5   98  30                                            468 1.0                                                                              80  70  65  5    5   60  25                                            469 1.0                                                                              90  70  75  0    5   65  40                                            470 1.0                                                                              15  80  75  5    0   75  5                                             471 1.0                                                                              75  90  95  70   10  100 20                                            472 1.0                                                                              50  70  90  20   10  95  10                                            473 1.0                                                                              15  0   30  0    0   10  0                                             474 1.0                                                                              100 98  100 65   60  100 60                                            475 1.0                                                                              100 100 100 90   80  100 70                                            476 1.0                                                                              90  75  80  50   50  70  10                                            477 1.0                                                                              100 100 100 100  80  100 85                                            478 1.0                                                                              100 100 100 95   75  100 70                                            479 1.0                                                                              100 100 100 100  95  100 80                                            480 1.0                                                                              100 100 100 95   65  100 70                                            481 4.0                                                                              20  20  50  10   0   70  20                                            482 4.0                                                                              0   0   0   0    0   0   0                                             __________________________________________________________________________

Each compound listed in Table VI was also tested at the statedapplication rate for pre-emergence weed control as described above. Withthe exception of the compounds listed in Table VII below, the testedcompounds had no effect on the growth of the listed weed species, i.e.,had a 0 percent control rating, when applied pre-emergently.

                                      TABLE VII                                   __________________________________________________________________________    Pre-Emergence Testing                                                         Comp.                                                                             Rate                                                                      No. kg/ha                                                                            AVEFA                                                                             ECHCG                                                                             SETVI                                                                             ABUTH                                                                              IPOSS                                                                             SINAR                                                                             CYPES                                         __________________________________________________________________________    4   4.0                                                                              0   0   25  0    0   0   0                                             10  4.0                                                                              0   0   0   10   0   30  0                                             54  1.0                                                                              0   0   0   15   25  5   0                                             150 4.0                                                                              --  --  --  --   --  --  --                                            151 4.0                                                                              --  --  --  --   --  --  --                                            169 4.0                                                                              0   0   0   5    --  5   15                                            184 4.0                                                                              0   0   10  15   10  25  0                                             249 4.0                                                                              0   0   0   0    0   20  0                                             253 4.0                                                                              0   0   0   10   0   0   0                                             438 1.0                                                                              0   0   0   20   0   70  0                                             442 1.0                                                                              0   0   5   0    10  5   0                                             471 1.0                                                                              0   0   0   20   0   0   0                                             __________________________________________________________________________

The above data shows the post-emergence efficacy of the herbicidalcompounds and compositions of this invention, coupled with their safetyto plants when applied pre-emergently.

Although the invention has been described with reference to preferredembodiments and examples thereof, the scope of the present invention isnot limited only to those described embodiments. As will be apparent topersons skilled in the art, modifications and adaptations to theabove-described invention can be made without departing from the spiritand scope of the invention, which is defined and circumscribed by theappended claims.

What is claimed is:
 1. An herbicidal composition comprising:(A) anherbicidally effective amount of a compound of Formula (I) ##STR224##wherein n is 0, 1, 2, 3, 4, 5 or 6;R¹ is hydrogen, hydroxy, C₁ -C₄alkoxy, halogen, C₁ -C₄ alkyl, C₁ -C₄ haloalkyl, hydroxy-C₁ -C₄ -alkyl,hydroxy-C₁ -C₄ -alkoxy or N(R⁸)(R⁹) wherein R⁸ and R⁹ are eachindependently hydrogen or C₁ -C₃ alkyl; each R², R³, R⁴ and R⁵ isindependently hydrogen; hydrocarbyl; substituted hydrocarbyl;hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbyl-S(O)m--; orsubstituted hydrocarbyl-S(O)_(m) --; R⁶ and R⁷ are each independentlyhydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy;substituted hydrocarbyloxy; hydrocarbyl-S(O)_(m) --; substitutedhydrocarbyl-S(O)_(m) --; pyridyl; substituted pyridyl; or are of theformula N(R¹²)(R¹³) wherein R¹² and R¹³ are independently hydrogen,hydrocarbyl or substituted hydrocarbyl; or R⁶ and R⁷ together with thenitrogen to which they are bound form an aziridine; piperazine;morpholine; thiomorpholine; thiomorpholine sulfinyl; thiomorpholinesulfonyl; hexamethyleneimine; piperidine, tetrahydropyridine; pyrazole;imidazole; pyrrole; triazole; tetrahydropyrimidine; dihydroimidazole;pyrroline; azetidine; perhydroindole; perhydroquinoline;perhydroisoquinoline or pyrrolidine ring; any of which may be optionallysubstituted with C₁ -C₁₂ alkyl, halo, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁-C₅ haloalkyl, C₆ -C₁₀ aryl, C₆ -C₁₀ aryl substituted with halo or C₁-C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆ arylalkyl substituted with halo orC₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀ alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀alkylthio, C₁ -C₁₀ alkylsulfonyl, phenoxy, phenoxy substituted with haloor C₁ -C₆ alkyl, C₂ -C₁₀ alkenyl or cyano; or R⁴ and R⁶ or R² and R⁶together with the nitrogen and carbon atoms to which they are bound forman aziridine; piperazine; morpholine, thiomorpholine; thiomorpholinesulfinyl; thiomorpholine sulfonyl; hexamethyleneimine; piperidine,tetrahydropyridine; pyrazole; imidazole; pyrrole; triazole,tetrahydropyrimidine; dihydroimidazole; pyrroline; azetidine;perhydroindole; perhydroquinoline; perhydroisoquinoline; or pyrrolidinering; any of which may be optionally substituted with C₁ -C₁₂ alkyl,hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆ -C₁₀ aryl, C₆-C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇-C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁-C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or R² and R⁴ together with the carbon atoms to which they arebound form a C₅ -C₆ cycloalkyl or cycloalkenyl ring; any of which may beoptionally substituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ arylsubstituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or R⁴ and R⁵ together form a 3-6 membered carbocyclic ring,optionally substituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆alkoxy, C₁ -C₆ alkylthio or N(R¹⁰)(R¹¹) wherein R¹⁰ and R¹¹ are eachindependently hydrogen or C₁ -C₁₂ alkyl; and m is 0, 1 or 2; or anagrochemically acceptable salt or hydrolyzable ester thereof; with theproviso that when n is 0, R⁴ and R⁵ are both hydrogen and R⁶ and R⁷ areboth --C₂ H₅, R¹ is not --NH₂ ; and (B) an agrochemically acceptablecarrier therefor.
 2. A composition according to claim 1, wherein R¹ ishydrogen or hydroxy.
 3. A composition according to claim 1, wherein R²,R³, R⁴ and R⁵ are independently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenylor C₆ -C₁₀ aralkyl optionally substituted with halogen or hydroxy.
 4. Acomposition according to claim 1, wherein R⁶ and R⁷ are eachindependently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl, or C₆ -C₁₀ aralkyloptionally substituted with halogen or hydroxy.
 5. A compositionaccording to claim 1, wherein R⁴ and R⁵ together with the nitrogen andcarbon atoms to which they are bound form a pyrrolidine or piperidinering, either of which may be optionally substituted with halogen,hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl.
 6. A composition according toclaim 1, wherein R⁶ and R⁷ together with the nitrogen to which they arebound form a pyrrolidine or piperidine ring, either of which may beoptionally substituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆alkyl.
 7. A composition according to claim 1, wherein n is 0 or
 1. 8. Acomposition according to claim 1, whereinR¹ is hydrogen, hydroxy,halogen or C₁ -C₄ alkyl; R², R³, R⁴ and R⁵ are independently hydrogen;C₁ -C₁₂ alkyl; C₂ -C₁₂ alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl,halo-C₂ -C₁₂ alkenyl; halo-C₂ -C₁₂ -alkynyl; C₆ -C₁₄ aralkyl; C₁ -C₁₂alkoxy; or C₁ -C₁₂ alkylthio; R⁶ and R⁷ are independently hydrogen; C₁-C₁₂ alkyl; C₂ -C₁₂ alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl;halo-C₂ -C₁₂ alkenyl; halo-C₂ -C₁₂ alkynyl; pyridyl; substitutedpyridyl; phenyl; substituted phenyl; C₆ -C₁₄ aralkyl; substituted C₆-C₁₄ aralkyl; C₁ -C₁₂ alkoxy or C₁ -C₁₂ alkylthio; or R² and R⁴ togetherwith the carbon atoms to which they are bound form an optionallysubstituted C₅ -C₆ cycloalkyl or cycloalkenyl ring; or R⁴ and R⁶together with the nitrogen and carbon atoms to which they are bound forma 3- to 7-membered ring optionally substituted with halogen, hydroxy, C₁-C₆ alkyl, C₁ -C₆ alkylthio or C₇ -C₁₆ aralkyl; or R⁶ and R⁷ togetherwith the nitrogen to which they are bound form a 3- to 7-membered ring,optionally substituted with halogen, hydroxy, C₁ -C₆ alkoxy, nitro, C₁-C₆ alkyl, C₇ -C₁₆ aralkyl or C₁ -C₆ alkylthio groups; and n is 0, 1, 2or
 3. 9. A composition according to claim 1, whereinR¹ is hydrogen orhydroxy; R² and R³ are hydrogen; R⁴ and R⁵ are each independentlyhydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl or C₆ -C₁₀ aralkyl optionallysubstituted with halogen or hydroxy; and R⁶ and R⁷ are eachindependently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl, or C₆ -C₁₀ aralkyloptionally substituted with halogen or hydroxy; or R⁴ and R⁶ togetherwith the nitrogen and carbon atoms to which they are bound form apyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl; or R⁶and R⁷ together with the nitrogen to which they are bound form apyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl; and nis 0 or
 1. 10. A method of controlling the growth of plants comprisingapplying to the locus of such plants an herbicidally effective amount ofa compound of the Formula (I): ##STR225## wherein n is 0, 1, 2, 3, 4, 5or 6;R¹ is hydrogen, hydroxy, C₁ -C₄ alkoxy, halogen, C₁ -C₄ alkyl, C₁-C₄ haloalkyl, hydroxy-C₁ -C₄ -alkyl, hydroxy-C₁ -C₄ -alkoxy orN(R⁸)(R⁹) wherein R⁸ and R⁹ are each independently hydrogen or C₁ -C₃alkyl; each R², R³, R⁴ and R⁵ is independently hydrogen; hydrocarbyl;substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; or substituted hydrocarbyl-S(O)_(m) --; R⁶ andR⁷ are each independently hydrogen; hydrocarbyl; substitutedhydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy;hydrocarbyl-S(O)_(m) --; substituted hydrocarbyl-S(O)_(m) --; pyridyl;substituted pyridyl; or are of the formula N(R¹²)(R¹³) wherein R¹² andR¹³ are independently hydrogen, hydrocarbyl or substituted hydrocarbyl;or R⁶ and R⁷ together with the nitrogen to which they are bound form anaziridine; piperazine; morpholine; thiomorpholine; thiomorpholinesulfinyl; thiomorpholine sulfonyl; hexamethyleneimine; piperidine,tetrahydropyridine; pyrazole; imidazole; pyrrole; triazole;tetrahydropyrimidine; dihydroimidazole; pyrroline; azetidine;perhydroindole; perhydroquinoline; perhydroisoquinoline or pyrrolidinering; any of which may be optionally substituted with C₁ -C₁₂ alkyl,halo, hydroxy, C₁ -C₁₀ hydroxyalkyl, C₁ -C₅ haloalkyl, C₆ -C₁₀ aryl, C₆-C₁₀ aryl substituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇-C₁₆ arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁-C₁₀ -alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or R⁴ and R⁶ or R² and R⁶ together with the nitrogen andcarbon atoms to which they are bound form an aziridine; piperazine;morpholine, thiomorpholine; thiomorpholine sulfinyl; thiomorpholinesulfonyl; hexamethyleneimine; piperidine, tetrahydropyridine; pyrazole;imidazole; pyrrole; triazole, tetrahydropyrimidine; dihydroimidazole;pyrroline; azetidine; perhydroindole; perhydroquinoline;perhydroisoquinoline; or pyrrolidine ring; any of which may beoptionally substituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ arylsubstituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀-alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or R² and R⁴ together with the carbon atoms to which they arebound form a C₅ -C₆ cycloalkyl or cycloalkenyl ring; any of which may beoptionally substituted with C₁ -C₁₂ alkyl, hydroxy, C₁ -C₁₀hydroxyalkyl, C₁ -C₅ haloalkyl, halo, C₆ -C₁₀ aryl, C₆ -C₁₀ arylsubstituted with halo or C₁ -C₆ alkyl, C₇ -C₁₆ arylalkyl, C₇ -C₁₆arylalkyl substituted with halo or C₁ -C₆ alkyl, nitro, halo-C₁ -C₁₀-alkyl, C₁ -C₁₀ alkoxy, C₁ -C₁₀ alkylthio, C₁ -C₁₀ alkylsulfonyl,phenoxy, phenoxy substituted with halo or C₁ -C₆ alkyl, C₂ -C₁₀ alkenylor cyano; or R⁴ and R⁵ together form a 3-6 membered carbocyclic ring,optionally substituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆alkoxy, C₁ -C₆ alkylthio or N(R¹⁰)(R¹¹) wherein R¹⁰ and R¹¹ are eachindependently hydrogen or C₁ -C₁₂ alkyl; and m is 0, 1 or 2; or anagrochemically acceptable salt or hydrolyzable ester thereof; with theproviso that when n is 0, R⁴ and R⁵ are both hydrogen and R⁶ and R⁷ areboth --C₂ H₅, R¹ is not --NH₂.
 11. A method according to claim 10,wherein R¹ is hydrogen or hydroxy.
 12. A method according to claim 10,wherein R², R³, R⁴ and R⁵ are independently hydrogen, C₁ -C₈ alkyl, C₂-C₈ alkenyl or C₆ -C₁₀ aralkyl optionally substituted with halogen orhydroxy.
 13. A method according to claim 10, wherein R⁶ and R⁷ are eachindependently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl, or C₆ -C₁₀ aralkyloptionally substituted with halogen or hydroxy.
 14. A method accordingto claim 10, wherein R⁴ and R⁵ together with the nitrogen and carbonatoms to which they are bound form a pyrrolidine or piperidine ring,either of which may be optionally substituted with halogen, hydroxy, C₁-C₆ alkoxy or C₁ -C₆ alkyl.
 15. A method according to claim 10, whereinR⁶ and R⁷ together with the nitrogen to which they are bound form apyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl.
 16. Amethod according to claim 10, wherein n is 0 or
 1. 17. A methodaccording to claim 10, whereinR¹ is hydrogen, hydroxy, halogen or C₁ -C₄alkyl; R², R³, R⁴ and R⁵ are independently hydrogen; C₁ -C₁₂ alkyl; C₂-C₁₂ alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl, halo-C₂ -C₁₂ alkenyl;halo-C₂ -C₁₂ -alkynyl; C₆ -C₁₄ aralkyl; C₁ -C₁₂ alkoxy; or C₁ -C₁₂alkylthio; R⁶ and R⁷ are independently hydrogen; C₁ -C₁₂ alkyl; C₂ -C₁₂alkenyl; C₂ -C₁₂ alkynyl; halo-C₁ -C₁₂ alkyl; halo-C₂ -C₁₂ alkenyl;halo-C₂ -C₁₂ alkynyl; pyridyl; substituted pyridyl; phenyl; substitutedphenyl; C₆ -C₁₄ aralkyl; substituted C₆ -C₁₄ aralkyl; C₁ -C₁₂ alkoxy orC₁ -C₁₂ alkylthio; or R² and R⁴ together with the carbon atoms to whichthey are bound form an optionally substituted C₅ -C₆ cycloalkyl orcycloalkenyl ring; or R⁴ and R⁶ together with the nitrogen and carbonatoms to which they are bound form a 3- to 7-membered ring optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkyl, C₁ -C₆ alkylthio or C₇-C₁₆ aralkyl; or R⁶ and R⁷ together with the nitrogen to which they arebound form a 3- to 7-membered ring, optionally substituted with halogen,hydroxy, C₁ -C₆ alkoxy, nitro, C₁ -C₆ alkyl, C₇ -C₁₆ aralkyl or C₁ -C₆alkylthio groups; and n is 0, 1, 2 or
 3. 18. A method according to claim10, whereinR¹ is hydrogen or hydroxy; R² and R³ are hydrogen; R⁴ and R⁵are each independently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl or C₆ -C₁₀aralkyl optionally substituted with halogen or hydroxy; and R⁶ and R⁷are each independently hydrogen, C₁ -C₈ alkyl, C₂ -C₈ alkenyl, or C₆-C₁₀ aralkyl optionally substituted with halogen or hydroxy; or R⁴ andR⁶ together with the nitrogen and carbon atoms to which they are boundform a pyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl; or R⁶and R⁷ together with the nitrogen to which they are bound form apyrrolidine or piperidine ring, either of which may be optionallysubstituted with halogen, hydroxy, C₁ -C₆ alkoxy or C₁ -C₆ alkyl; and nis 0 or 1.